HIV Reservoir in Naive CD4 PDF Print E-mail
Written by Alain Lafeuillade   
Thursday, 11 November 2010 20:27

Both CD31(+) and CD31(-) Naive CD4(+) T Cells Are Persistent HIV Type 1-Infected Reservoirs in Individuals Receiving Antiretroviral Therapy.

Wightman F, Solomon A, Khoury G et al. J Infect Dis. 2010 Dec 1; 202(11): 1738-48. Epub 2010 Oct 27.

A
lthough most of the reservoir resides in memory CD4+ T cells, naive cells are also infected at a lower frequency. In this study, the authors have analyzed the ratio between CD31+ and CD31- naive CD4+ T cells in different populations of patients infected with HIV.

 

 

T
he expression of CD31 on naive T cells therefore marks a naive T cell that has not yet undergone significant homeostatic proliferation. Recent evidence also suggests that CD31+ naive T cells can proliferate in response to IL-7 alone without losing expression of CD31. Expression of CD31 is not the perfect marker for a recent thymic emigrant (RTE) but rather represents a subset of naive CD4+ T cells that are “enriched” for RTE and have not significantly proliferated after exit from the thymus.

 

T
his report contains both a cross-sectional (n=94) and longitudinal (n=10) study of HIV-infected patients before and after ART.

 

Infected naive CD4+ T cells represent a stable and possibly expanding reservoir in patients receiving ART.

In individuals receiving ART, the percentage of naive CD4+ T cells expressing CD31 was significantly higher than in normal control subjects (P= .007) or patients naive to ART (P<.001). There was a positive correlation between CD4+ T cell count and the percentage of CD31+ naive T cells for untreated but not for treated patients (P= .009 and .83, respectively; Spearman r=0.51 and -0.03).
A significantly higher concentration of HIV-1 DNA was found in memory than in CD31+ naive CD4+ T cells (P= .004) but no difference between memory and CD31- naive CD4+ T cells (P= .14). The concentration of HIV-1 DNA in CD31- naïve CD4+ T cells was not significantly different from that in CD31+ naive CD4+ T cells (P= .11).
After ART initiation, a significant decline in HIV-1 DNA copies per 1 million memory CD4+ T cells was observed, although there was no change in the concentration of HIV-1 DNA in either CD31+ or CD31- naive CD4+ T cells.

These data would be consistent with a post-ART expansion in both infected and uninfected naive T cells.

 

When the absolute numbers of infected cells per microliter of blood were compared before and after 24 months of ART, the absolute number of infected memory CD4+ T cells was significantly lower (P= .04); there were significantly more HIV-1–infected CD31+ naive CD4+ T cells (P= .04) and no significant change in the number of HIV-1–infected CD31- naive CD4+ T cells (P= .49) after 24 months. At 24 months after the initiation of ART, infected naive T cells made a larger contribution to the overall number of infected CD4+ T cells than before ART. These data would be consistent with a post-ART expansion in both infected and uninfected naive T cells.

C
onsequently, Both CD31+ and CD31- naive CD4+ T cells are infected in HIV-1–patients in vivo, and both subsets represent a very stable reservoir in patients receiving ART.
Although few in absolute number, infected naive CD4+ T cells represent a stable and possibly expanding reservoir in patients receiving ART. Specific strategies that target the naive T cell reservoir should be further explored in future studies of HIV-1 eradication.
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Key words: cd4, eradication, hiv, naive, reservoir
Last Updated on Friday, 19 November 2010 17:09
 

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