PD-1 long-term nonprogressors (LTNP) and new china discovery 1 June 2007

[bimazek]

Basically this says many things but most important is.... PD-1 is High in HIV-specific CD8 T cells in typical disease progressors (TPs) but not in long-term nonprogressor (LTNP) patients.  This means that all people who do not get sick from HIV is because their PD-1 never turns to the high state so that means the CD8 cell never gets turned off by pd-1 .

this graph shows everything... this shows why the hiv   CD8   pd-1 interactions are so complex, because the process is very complex., this is why disease progression is complex as to when or how fast it progresses
here will be the future long term solution i believe because now for first time science understands the entire process of why the cd8 cells do not do thier job as they do in other animals...

http://bloodjournal.hematologylibrary.org/content/vol109/issue11/images/large/zh80110704370001.jpeg

Antigen-presenting cells (APCs)

HIV-1 disease progression, and the defects are reversible because inhibition of HIV-1 viremia by HAART restores virus-specific CD8 T cells with reduced PD-1 expression. This highlights PD-1/PD-L1 interaction as a potential therapeutic target for chronic HIV-1 infection. It is possible to recover HIV-specific T-cell functions either by reducing viremia or by blockading PD-1/PD-L1 interaction.

one thing i must disagree with in this article is that they say... is the idea that a once a week pd-1 inhibitor cannot do good


http://bloodjournal.hematologylibrary.org/cgi/content/full/109/11/4593


Blood, 1 June 2007, Vol. 109, No. 11, pp. 4593-4594.

PD-1 is up-regulated on HIV-specific CD8 T cells in typical disease progressors (TPs) but not in long-term nonprogressor (LTNP) patients,
 
PD-1+ T cells: exhausted and premature?

UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL

PD-1 up-regulation is correlated with the exhaustion of virus-specific CD8 T cells in people chronically infected with HIV-1. Zhang and colleagues report that PD-1 is up-regulated on HIV-specific CD8 T cells in typical disease progressors (TPs) but not in long-term nonprogressor (LTNP) patients, and PD-1 expression is down-regulated in HIV-1 patients with successful response to HAART therapy.

Zhang and colleagues report that PD-1 is up-regulated on human immunodeficiency virus (HIV)–specific CD8 T cells in typical disease progressors (TPs) but not in long-term nonprogressor (LTNP) patients. PD-1 up-regulation is associated with reduced expression of CD8 effectors perforin and IFN-, and decreased T-cell proliferation. Of interest, as blockade of PD-1 with anti–PD-L1 mAb in vitro restores effector functions of CD8 T cells, HIV-1 patients with successful response to highly active antiretroviral therapy (HAART) appear to also restore HIV-specific CD8 T cells in vivo.


These findings suggest that sustained PD-1 expression on HIV-specific CD8 T cells depends on active HIV-1 viremia, and reducing viremia with HAART can reverse the defects associated with PD-1 expression in HIV-specific CD8 T cells.
 
The inhibitory receptor PD-1 is rapidly up-regulated on activated T cells (reviewed in Sharpe et al5). Its expression is decreased on effector T cells and diminished on memory T cells after antigen clearance.

THIS IS WHY THINGS CAN BE VERY BAD VERY FAST IN HIV DISEASE...
Upon antigen restimulation, effector T cells also up-regulate expression of PD-1. Therefore, sustained stimulation of naive and/or effector T cells during chronic virus infection will lead to accumulation of PD-1+ T cells.


Antigen-presenting cells (APCs) in HIV-1–infected patients express high levels of PD-L1 or B7-H1.6


It is likely that impaired APCs with PD-L1 may help sustain PD-1 expression on T cells and impair their effector maturation, and allow chronic viral infection (see figure).     

[hahaha]

Being a Chinese, I mean Taiwanese, I try to search related articles but fail.  It seems that Chinese government treat this as top secret and has not yet disclosed to the public any progress they have.  But I really cross my finger and wish in the very near future, an vaccine of immunetherapy would be born..........

I hate sustiva......

 

[J220]

The good news is that I believe the Chinese government would just LOVE to upstage the Western world, and be the one to come up with a cure for HIV. This conceivably could turn out to be the case. Fingers crossed.