PPHM and Tarvacin discussion

[Kharma]

Yep Precious, Quite the contributor. These are your last posts on RB(not counting the ones which were deleted) before you got kicked off again. Your Stewart ID below shows no posts because all of those were so foul they got deleted and you were tosed again with that ID. That is very difficult to do. Just have to follow the rules. OOPs--don't forget the Hezekiah ID also. These are all ID's you CONTRIBUTED with after you got tosed with your precious ID. But then you say you never got tosed and can post there anytime Riiiiiiiight Very Very impressive precious. I hope you take note that I am not bashing or calling you any names precious. Just showing history in your words. We could be civil here, that is a point I have been trying to make. Hate to see you call Katie, Terry and others all those names. No one else resorts to name calling.


http://ragingbull.quote.com/mboard/m...otechinvestor1

http://ragingbull.quote.com/mboard/m...ewrb_the_moron

http://ragingbull.quote.com/mboard/m...r=hezekiah2k20

Kharma.........catching up with you son

[Preciouslife1]

Playing tennis with a loser am I??? Funny little man this bad Kharma whose whole agenda is foul yet throws stones from his glass house...BAD KHARMA....why don't you post all the posts that were attacking me instead of just my responses in the name of fairness and correctness??Because that would take months to do and you aren't about integrity nor fairness, you are a paid basher and a moroff, quite simple...dismissed...your serve insane one.

[Kharma]

Tried to warn you Precious. But you seem to have outdone even my expectations. No JAIL time for you on IHUB. It appears as those you have made history with being the first to be banned from the PPHM Board. WOW!!!!!!!!!!!!!!!!! No posting priveleges IHUB or RB. Very tough to do. Now that you cannot post on those boards I might be limiting my posts. We will see.

http://www.investorshub.com/boards/s...?board_id=2076
Kharma..........definitely catching up with you son!

[Preciouslife1]

Kharma = AKScrub.

Thank you for giving yourself away there scrub!!
By: AKcub29 Aug 2006, 05:23 PM EDTMsg. 212066 of 212071
(This msg. is a reply to 212063 by odd_sod.)
Jump to msg. # </STRONG>Agreed Bob. And now that Precious can't last more than a day on RB anymore, which is good, but he sure has been stirring it up over on IHUB. It has been taken to his board though by this fellow named Kharma (appropriately). Kind of comical goings on over there for anyone that likes that sort of entertainment.

http://ihub.org/forum/showthread.php?p=2113&posted=1#post2113

Cub

How apropos that you sign off as "cub" as the Cubbies are perennial losers and has beens. AKSCRUB the self appointed self righteous, pompous, arrogant attacker and one who NEVER contributes towards anyone else's knowledge base nor understanding of anything related to PPHM...to wit...http://www.investorshub.com/boards/profile.asp?User=14020...

Posted by: AlaskaCub
In reply to: A deleted messageDate:5/26/2006 2:25:56 PM
Post #of 8341
Hello Moderators

Just wanted to let you know I emailed Matt with TOS violations on PL1's posts. I hate to clog up the board with this type of post but I am really getting tired of his posts. Have been for quite some time. There is no place at all for PL1's ramblings and attacks on this board period. I am hoping that others will report TOS and perhaps Matt can help clean up this board with a little jail time for PL1. He has been asked time and time again to refrain.

Thanks

AKcub
************************************************** **

Posted by: AlaskaCub
In reply to: A deleted messageDate:5/26/2006 1:49:09 PM
Post #of 8341
I hope the moderators leave your post up PL1 so that more of the readers here will have a chance to click on the TOS button. If more would do that perhaps it will slim down our moderators workload.

Thanks

************************************************** *****

The Scrub, the self appointed board policeman....what a joke of a human doing you are!!

[Preciouslife1]

How swiftly the strained honey
of afternoon light
flows into darkness

and the closed bud shrugs off
its special mystery
in order to become a blossom

as if what exists, exists
so that it can be lost
and become PRECIOUS......

[Kharma]

Nope precious... but we do have an awful lot in common. Better to be considered Cub than Rico and a few others you have thought me to be. I am curious about your thoughts on the ban(Looks like Cub ran a pretty effective campaign after all )? You get awful excited trying to figure out who I am. Try being civil and reply please.

Ban List for PEREGRINE PHARMACEUTICALS

Alias Ban Date BannedBy
Preciouslife 18/29/2006 4:11:44 PM 2744

Kharma.......absolutely catching up with you son

[Preciouslife1]

My serve there and Kharma is something that I subscribe to NOT...My Lord does not project Karma nor does karma have anything to do with ignorance of mass internet cyberterrorism that you neonazi's employ. I do not need that IHUB and you are incorrect as I can post on that moronic RB, but choose to not propigate more posts on a dead medium....Kharma catching up to me??? Funny, but life here in SRQ is pretty amazing and being in such a blessed environment is simply amazing and awesome....but you will most likely never know that Bad Kharma....keep your lilly white IHUB environment where mundane and inane posts stay, but true information gets quashed....losers that do not understand the potential collaborations of what I am posting....Ah well, my shares will appreciate to the stratosphere and many will get blessed from the proceeds, and unlike you, I most assuredly am not greedy nor in this for the money.....naziman.

[Preciouslife1]

OOPS AKSCRUB...
OT: Hey Bob--Two boards are now Precious free.

Oops! That message number is invalid on this board.
That message may have been removed, or you clicked an invalid link. We suggest you return to the PPHM index page.

So, it looks like your rudeness is garnering attention there scrub!!!
Looks like your "kharma" is coming home to roost..there turkey!

[Kharma]

Is that the best you can do Precious. Oh well.... I sure would like to see one post just one post that doesn't involve name calling. Until then, I believe my job is done. One last thing which I believe I have proven to the readers........................................... ..
You Cannot Post On RB with any of your past aliases as you have been banned there as well!!!!!!!!!!!!!!

Kharma.....caught up with you son

[Preciouslife1]

Nope dope!!! Your akscrub ID that signs off with a "cub" says it all...a baby bear...not a real bear, not a winner, but rather a loser in a magnitude of gigantic proportion.....hope this makes you feel like a real man, cause that will never happen in real life as cowards and liars who say they will not post here again only to vomit all over a science site with a rotten personal agenda, can never feel what it is to be a real man...cowardly little cub...hahaha!

[Preciouslife1]

Nanoparticles and siRNA – Partners on the Pathway to New Cancer Therapies
Seven short years ago, in an October 1999 paper published in the journal Science, the research community learned of a radically new mechanism that cells can use to control protein production. Discovered by plant geneticists David Baulcombe, Ph.D., and Andrew Hamilton, Ph.D., this new process relied on small pieces of double-stranded RNA molecules that could bind to and neutralize specific messenger RNA molecules, which then prevented the cell from translating that particular message into a protein. Then, in early 2002, a paper in Nature from Thomas Tuschl, Ph.D., and his collaborators at the Max-Planck Institute for Biophysical Chemistry in Gottingen, Germany, showed that small interfering RNA (siRNA) molecules could block protein production in mammalian cells.
What is an siRNA?
siRNAs have a well-defined structure: a short (usually 21-nucleotide-long) double-strand of RNA (dsRNA) with 2-nucleotide 3' overhangs on either end:

Each strand has a 5' phosphate group and a 3' hydroxyl (-OH) group. This structure is the result of processing by an enzyme that converts either long dsRNAs or hairpin RNAs into siRNAs. siRNAs can also be introduced into cells using nanoparticles and other methods to bring about the specific knockdown of a gene of interest. Essentially any gene of which the sequence is known can thus be targeted based on sequence complementarity with an appropriately tailored siRNA. This method has made siRNAs an important tool for gene function and drug target validation studies in the post-genomic era.
Courtesy: Wikipedia http://en.wikipedia.org/wiki/SiRNA
Today, RNA silencing – the process triggered by siRNA molecules – is poised to have a major impact on the treatment of human ailments, particularly cancer. Using siRNA molecules, researchers believe they can turn off the ability of cancer cells to produce the key proteins that make them different from normal cells, and by doing so, stop malignancy in its tracks. Early proof-of-principle experiments in various tumor cells showed quickly that RNA silencing had great potential as a means for treating cancer.
But almost as soon as those early results were in, a major obstacle surfaced: The human body is well-equipped to destroy double-stranded RNA circulating in blood and prevent it from entering cells. As a result, getting these potential therapeutic agents to tumors and getting them into cancer cells was not going to be easy.
Enter nanotechnology. Nanoparticles, it turns out, are proving to be ideal carriers for siRNA molecules. “With nanoparticles, we have the ability to load large numbers of these molecules into a protected environment, target them to cancer cells, and then have them taken up efficiently by those cells and release the RNA molecules into the interior of those cells,” says Mark Davis, Ph.D., at the California Institute of Technology (Caltech).
In fact, the marriage between nanoparticles and siRNA is proving to be such a good one that several companies are already pushing nanoparticle-delivered anticancer siRNA agents toward human clinical trials. Intradigm, in Rockville, MD, expects to file an Investigational New Drug application with the U.S. Food and Drug Administration next year and begin clinical trials with its nanoparticulate formulation of an siRNA agent designed to stop tumor-associated angiogenesis. And in February of this year, Calando Pharmaceuticals, in Pasadena, CA, and the National Cancer Institute (NCI) entered into a collaborative development program for a nanoparticle-based siRNA therapeutic aimed at treating neuroblastoma, the most common extracranial solid tumor in children younger than five years old.
Targeting Is a Key

One characteristic of nanoparticles that has made them a favorite among cancer researchers in general, and not just those using siRNA, is the ability to decorate the surfaces of these drug vehicles with tumor-targeting agents. But with siRNA, this property is particularly attractive because there is some concern that siRNA delivered to the wrong cells may have unintended consequences. “The siRNA field itself is so young that we just aren’t sure yet how important it is to target just one particular type of cell,” says Vincent Rotello, Ph.D., of the University of Massachusetts in Amherst. “But the versatility of nanoparticles gives us the ability to better target cancer cells and to even develop nanoparticles that only deliver their RNA ***********************************s once they’ve entered the target cell. We hope that by taking advantage of these opportunities, that we can head off potential problems.”
At Caltech, for example, the Davis group has developed nanoparticles that provide effective release of their ***********************************s under the low pH conditions characteristic of intracellular environments experienced when nanoparticles enter cells via targeted cancer cell surface receptors. The resulting nanoparticles can carry significant amounts of chemically unmodified siRNA and effectively deliver them to targeted cells as his group showed in a paper published in Cancer Research last year. Davis, who is a founder of Calando and has licensed his lab’s work to the company, says he hopes to have an anticancer siRNA agent in clinical trials next year.
Meanwhile, Rotello and his colleagues are creating nanoparticles studded with molecules of folic acid, a well-studied nanoparticle targeting agent that binds to a receptor found in abundance on many types of cancer. But in addition, the surface of these nanoparticles is covered with a sulfur-containing chemical group known as a thiol, with the sulfur bonding to the surface of the gold nanoparticle. Cells contain large amounts of the molecule glutathione, which is also a thiol. The abundance of glutathione inside a cell results in the displacement of the thiols on the particle, triggering the release of the RNA payloads.
Peixuan Guo, Ph.D., at Purdue University’s Cancer Research Center, is taking advantage of another natural process to achieve targeted delivery and release of siRNA inside cancer cells. Nearly 20 years ago, Guo discovered that a particular bacteria-infecting virus called phi29 uses a novel type of RNA to package its DNA into its protein shell. Guo named his discovery pRNA, for packaging RNA, and today he and his colleagues are using it as a component of an all-RNA nanoparticle that resembles a triangle. Tests in both cultured human tumor cells and in mouse models of cancer have shown these RNA nanoparticles have potential as anticancer agents.


A triangular nanoparticle made of RNA carriers uses both folic acid and a receptor-binding aptamer as tumor-targeting agents to deliver anticancer siRNA molecules.
Courtesy: Peixuan Guo, Purdue University...........................End of Part #1

[Preciouslife1]

Guo's team created their nanoparticles by linking together two different kinds of RNA: pRNA, which acts as the delivery vehicle, and siRNA, which acts as the therapeutic agent. The team then added folic acid molecules as the targeting agent. “Using techniques we learned from our earlier work,” explains Guo, “we were able to combine [these molecules] into triangles that are between 25 and 40 nanometers wide. This is the Goldilocks size for any nanoparticle that is to be used in the body – not too big, not too small."
Particles larger than about 100 nanometers are generally too large to pass through cell membranes into the cell's interior, Guo says, and the body has a hard time retaining particles smaller than 10 nanometers. But the tiny triangles fit, and they worked well enough to interrupt the growth of human breast cancer cells and leukemia model lymphocytes in laboratory experiments. The use of such protein-free particles could avoid the induction of immune response and avoid antibody production and cell immunity. Therefore, it facilitates the long-term treatment in chronic diseases such as cancer, hepatitis B, or AIDS.


Simplified schematic of the key steps required for siRNA delivery to and function within mammalian cells.
Courtesy: Derek Bartlett and Mark Davis, Nucleic Acids Research and Oxford University Press. Nucleic Acids Res. 2006; 34(1): 322–333. Published online 2006 January 12. doi: 10.1093/nar/gkj439"One characteristic of cancer cells is that they do not stop growing, which is one reason tumors develop," Guo says. "Once inside, the siRNA essentially instructs the cells to 'stop not stopping.' The nanoparticles had done their work on the breast cancer cell cultures within a few days."
Additionally, the team found that the nanoparticles completely block cancer development in living mice. A group of mice that was in the process of developing cancer was tested with the nanoparticles, and they did not develop the disease. A second group, that was tested with mutated inactive RNA, all developed tumors.
"The results are very promising, but we still have several hurdles to jump before we can test this therapy on people," Guo says. "First and foremost, we must ensure that it is as safe as we think it is. Some RNA can be toxic to non-cancerous cells as well, and though our nanoparticles appear to go straight to the cancer cells, where we want them to go, we have to be sure they do not go anywhere else before we can inject them into a living person."
Stability of the RNA also is a factor the team must consider. Although his group had previously published data indicating that phi29 RNA nanoparticles are more stable than other RNA, Guo said the team has also introduced chemical modifications into the RNA backbone that further stabilizes it against degradation.
Intradigm’s approach to successfully deliver and target its lead anticancer siRNA agent is to use a multicomponent polymer system that self-assembles into a rugged nanoparticle when mixed with siRNA molecules. Martin Woodle, Ph.D., chief scientific officer at the company, leads the company’s efforts, which are aimed at developing an siRNA agent that silences the production of a receptor for vascular endothelial growth factor (VEGF) on the newly developing blood vessels surrounding tumors. The idea behind this approach is that if these blood vessels cannot respond to VEGF, angiogenesis will stop and tumors will not be able to procure the nourishment they need to thrive and ********************stasize.
Woodle and his colleagues start with the biocompatible polymer poly(ethyleneimine), or PEI, and link it to a second biocompatible polymer, poly(ethylene glycol), also known as PEG. As a targeting agent, the researchers chose a three-amino-acid peptide, arginine-glycine-aspartic acid (known by its amino acid code RGD) that binds to a class of proteins known as integrins. Found on the surface of new blood vessels, integrins are involved in a wide range of biological processes, including angiogenesis, tumor cell growth and ********************stasis, and inflammation. The researchers attached this integrin-targeting peptide to one end of the PEG polymer chain. They attached this targeting molecule to one end of the PEG polymer chain.
Mixing equal parts of the polymer-RGD construct and anti-VEGF receptor siRNA yields nanoparticles in which a core of PEI and siRNA is surrounded by a water-soluble shell of PEG, with the RGD-targeting peptide sticking out from the particle. Studies in cultured cells showed that this formulation entered only those cells containing integrins, suggesting that the RGD peptide was an effective targeting agent. In contrast, nanoparticles lacking RGD did not enter targeted cells. This study also showed that siRNA cargo was released within the cell and was able to silence VEGF receptor production.


Mice with Ewing’s sarcoma were treated with a targeted nanoparticle containing anti-tumor siRNA (#31-40), as well as various control formulations. Only the targeted agent had a marked effect on tumor growth. Tumors show up as purple areas.
Courtesy: Calando PharmaceuticalsNext, the Intradigm research team administered their nanoparticle to tumor-bearing mice; they also treated a second group of mice with a nanoparticle containing siRNA designed to silence a bacterial protein (to act as a control experiment) and left a third group of animals untreated. Within six days of intravenous injection, it was clear that the nanoparticle containing the anti-VEGF receptor siRNA was having the desired effect – tumor growth in the animals treated with that formulation was minimal, compared to significant growth seen in both of the two control groups. Intradigm hopes to begin clinical trials with this agent late next year.
Based on these results and others, the future of nanoparticle-based siRNA therapy for cancer looks promising. Certainly, questions remain concerning the safety of these agents, though clinical trials using siRNA to treat other illnesses have not yet come across any stop signs. Also, manufacturing RNA molecules is not trivial or inexpensive, though chemists have made marked improvements in reducing both the complexity and cost of RNA production.
“Obviously, all of these agents will have to prove themselves in clinical trials and until they do, they’ll remain in the promising but unproven category,” says Davis. “But combining siRNA with nanoparticle technology gives us a real opportunity to have an impact in the treatment of cancer."
—Joe Alper

[Preciouslife1]

New Method For Making Potential Cancer Fighter

Ras is a protein that works as a molecular switch, triggering biochemical events inside certain cells that lead to . The gene that produces ras gained notoriety as the first known oncogene -- a gene that can cause cancer.

Six years ago, Japanese scientists discovered that rasfonin, a compound isolated from a , selectively destroys ras-dependent cells. Normal cells were not harmed.
With the prospect that rasfonin could lead to a new family of anti-, scientists began searching for a way to make enough rasfonin for tests.
Scientists now are reporting development of that simpler method in a report scheduled for the Aug. 23 issue of the Journal of the American Chemical Society.
Robert K. Boeckman Jr. and colleagues explain that the only existing synthesis was complicated and not easily adapted for producing larger amounts of rasfonin. Their method involves only 16 steps (compared to 23 in the previous method) and produces 67 percent more rasfonin.
Reference: "Toward the development of a General Chiral Auxiliary. Enantioselective Alkylation and a New Catalytic Asymmetric Addition of Silyloxyfurans: Application to a Total Synthesis of (-)-Rasfonin." Journal of the American Chemical Society

[Preciouslife1]

Body's How The T Cells React To Parasitic Diseases

In the 1980s, the phrase “T cell count” burst into the world’s medical as thousands and then millions of patients died of The public began to understand the crucial importance of T cells—cellular Pac-Men that roam the bloodstream gobbling up attacks. and guarding against future

While scientists understood how T cells worked in certain kinds of diseases, one area has remained murky: disorders caused by protozoan . Now, because of a study just published and led by scientists at the ], researchers are closer than ever to understanding how T cells respond to parasitic diseases that kill millions each year.
“We have needed to really know what happens in these infections,” said Rick Tarleton, research professor of cellular biology and a faculty member in UGA’s Center for Tropical and Emerging Global Diseases (CTEGD). “What is the body’s response? This study is the first to show that one parasite, Trypanosoma cruzi, which causes Chagas Disease, elicits a T cell response focused on a few peptides, despite having some 12,000 genes capable of generating hundreds of thousands of potential targets for T cells.”
The study was just published in the online journal PLOS Pathogens, a peer-reviewed, open-access journal published by the Public Library of Science. Other authors of the paper include: Diana Martin, the lead author and postdoctoral fellow at UGA; former UGA Melissa Cabinian and Matthew Crim; computational biologist Brent Weatherly of the CTEGD; former UGA postdoctoral fellow Susan Sullivan; doctoral students Matt Collins, Charles Rosenberg and Sarah Craven; Alessandro Sette of the La Jolla Institute for Allergy and Immunology in San Diego, Ca.; and Susana Laucella and Miriam Postan of the Nacional de Laboratorios e Institutos de Salud in Buenos Aires, Argentina.
Chagas Disease is a tropical parasitic disease that sickens as many as 18 million people a year, mostly in the Americas, and kills 50,000 of those. The parasite that carries it, T. cruzi, is transmitted to mammals and humans through the bite of several genera of flying, biting insects. What intrigued Tarleton was that T cell response to infection from T. cruzi, while important to the body’s ability to fight disease, has remained somewhat cryptic because of the daunting complexity of the processes.
There are actually several kinds of T cells, and the ones Tarleton and his colleagues studied are the cytotoxic T cell, which scientists call CD8+. What they discovered is that the T cell response in T. cruzi is highly focused on a relatively small set of cellular features called “epitopes,” which are part of a macromolecule that is recognized by the immune system. The specific epitopes involved are ones encoded by the trans-sialidase (or “ts”) family of genes.
“The function of the ts genes is crucial for the parasite,” said Tarleton, “because the parasite must have sialic acids to invade cells and infect the host. But since it doesn’t have it, it must steal it from the host cells.” The problem is that T. cruzi potentially expresses more than a thousand ts genes, and this pool varies from parasite to parasite—making this set of proteins a poor choice for vaccine development, Tarleton said.
The importance of the new research, however, isn’t in specifically what happens in T. cruzi and Chagas Disease. Rather, it is a new understanding of how T cells react to infection in all parasitic diseases, including malaria, which may cause as many as 500 million infections and three million deaths annually in humans. The entire area has been little understood because of the almost impenetrable complexity of the problem.
In organisms like viruses and bacteria, which have relatively small genomes, analysis can be more direct; however, understanding the targets of the T cell response in complex pathogens such as T. cruzi requires much more. Scientists must integrate information generated from the recent analysis of the T. cruzi genome and proteome, with bioinformatics and cutting-edge techniques like advanced flow cytometry to unravel what is happening.
Grant support for the research came from the National Institutes of Health.

[Preciouslife1]

J Immunol. 2006 Sep 1

Cooperative induction of a tolerogenic dendritic cell phenotype by cytokines secreted by pancreatic carcinoma cells.


Ag presentation by dendritic cells (DC) is essential to effective antitumor T cell responses in cancer patients. Depending on their origin, maturation state, and the ambient cytokine milieu, DC can differentiate into distinct subpopulations, which preferentially either induce Th1 cell activation (CD11c(+),CD123(-) myeloid DC (MDC)) or immunosuppressive T cell development (CD11c(-),CD123(+) plasmacytoid DC (PDC)). The present study was undertaken to characterize the effects of pancreatic carcinoma cell-derived cytokines on immature monocyte-derived DC (iMo-DC) in vitro and in vivo. Medium conditioned by human pancreatic carcinoma cells inhibited iMo-DC proliferation, expression of costimulatory molecules (CD80 and CD40) and of HLA-DR, and functional activity as assessed by MLR and IL-12p70 production. iMo-DC generated from pancreatic carcinoma patients in advanced stages of the disease similarly showed decreased levels of HLA-DR expression and reduced ability to stimulate MLR in response to CD40L and IFN-gamma. Moreover, in tumor-patient peripheral blood, the ratio of MDC to PDC cells was lower than in healthy controls due to reduced numbers of MDC CD11c(+) cells. Importantly, rather than a single cytokine, a combination of tumor-derived cytokines was responsible for these effects; these were primarily TGF-beta, IL-10, and IL-6, but not vascular endothelial growth factor. In summary, we have identified an array of pancreatic carcinoma-derived cytokines that cooperatively affect iMo-DC activation in a manner consistent with ineffective antitumor immune responses.

CONTEXT:

Interaction between Phosphatidylserine and the Phosphatidylserine Receptor Inhibits Immune Responses In Vivo
The Journal of Immunology, 2005, 174: 1393-1404.


Interactions between macrophages and apoptotic cells result in the secretion of anti-inflammatory mediators such as TGF-{beta}, IL-10, and PGE2, as well as inhibition of the production of proinflammatory mediators


Data derived from experiments in vitro and in vivo suggest that PS exposure is crucial for the release of TGF-{beta} by phagocytes that accompanies apoptotic cell recognition and uptake (11, 37, 38). Furthermore, PS-containing liposomes can mimic the response to apoptotic cells by generating TGF-{beta} release (11, 38). Blocking PS on apoptotic cells with annexin V (a Ca2+-dependent, PS-binding protein) has been shown to eliminate the inhibitory effects of the apoptotic cells on the humoral responses (39).


Phosphatidylserine Regulates the Maturation of Human Dendritic Cells
The Journal of Immunology, 2006, 176: 4573-4580.

we hypothesized that PS might play a role in the inhibition of myeloid DC maturation. To test this hypothesis, we prepared large unilamellar liposomes containing PS as a simplified model of cell membrane alterations associated with apoptosis. We examined the effect of PS containing liposomes on DC maturation and immunostimulatory capacity. Our results suggest that PS inhibits the ability of DCs to undergo maturation, secrete IL-12, activate T cells, and stimulate IFN-{gamma}-producing CD4+ T cells

We found that PS, which is recognized specifically by DCs, triggers phagocytosis and plays a key role in modulating DC maturation and function


...PS did not simply inhibit the ability to activate T cells, but selectively modulated the ability to induce IFN-{gamma}-producing T cells


...PS exposure directly inhibits DC maturation and modulates their ability to activate T cell responses. PS is specifically recognized by DCs and triggers phagocytosis via the PSR. Our findings suggest that PS modulates the adaptive immune response at three different levels: 1) PS inhibits survival, Ag presentation, and costimulation by DCs, leading to ineffective T cell proliferation; 2) PS inhibits IL-12p70 secretion by DCs, diminishing the ability to stimulate IFN-{gamma}-producing T cells characteristic of Th1 responses; and 3) DCs exposed to PS have reduced ability to stimulate the proliferation of activated CD8+ T cells, even in the presence of abundant Ags. PS may synergize with additional signals, such as CD200, IL-10, and TGF-{beta}, expressed by apoptotic, inflammatory, or stromal cells (20, 22, 50, 51, 56, 65, 66). Further understanding of the mechanisms by which PS modulates DC function may lead to the development of effective immunotherapies for autoimmune diseases and for cancer.


jazzbeerman....