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Potential role for HIV-specific CD38-/HLA-DR+ CD8+ T cells in viral suppression and cytotoxicity in HIV controllers.


ABSTRACT:

Background

HIV controllers (HIC) are rare HIV-1-infected patients who exhibit spontaneous viral control. HIC have high frequency of CD38-/HLA-DR+ HIV-specific CD8+ T cells. Here we examined the role of this subset in HIC status.

Materials and methods

We compared CD38-/HLA-DR+ CD8+ T cells with the classical CD38+/HLA-DR+ activated phenotype in terms of 1) their activation status, reflected by CD69, CD25, CD71, CD40 and Ki67 expression, 2) functional parameters: Bcl-2 expression, proliferative capacity, and IFN-γ and IL-2 production, and 3) cytotoxic activity. We also investigated how this particular profile is generated.

Results

Compared to CD38+/HLA-DR+ cells, CD38-/HLA-DR+ cells exhibited lower expression of several activation markers, better survival capacity (Bcl-2 MFI, 367 [134-462] vs 638 [307-747], P = 0.001), higher frequency of polyfunctional cells (15% [7%-33%] vs 21% [16%-43%], P = 0.0003), greater proliferative capacity (0-fold [0-2] vs 3-fold [2]-[11], P = 0.007), and higher cytotoxicity in vitro (7% [3%-11%] vs 13% [6%-22%], P = 0.02). The CD38-/HLA-DR+ profile was preferentially generated in response to low viral antigen concentrations.

Conclusions

These data highlight the role of CD38-/HLA-DR+ HIV-specific CD8+ T cell cytotoxicity in HIC status and provide insights into the mechanism by which they are generated. Induction of this protective CD8+ subset may be important for vaccine strategies.

SUBMITTER: Hua S 

PROVIDER: S-EPMC4084978 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Potential role for HIV-specific CD38-/HLA-DR+ CD8+ T cells in viral suppression and cytotoxicity in HIV controllers.

Hua Stéphane S   Lécuroux Camille C   Sáez-Cirión Asier A   Pancino Gianfranco G   Girault Isabelle I   Versmisse Pierre P   Boufassa Faroudy F   Taulera Olivier O   Sinet Martine M   Lambotte Olivier O   Venet Alain A  

PloS one 20140707 7


<h4>Background</h4>HIV controllers (HIC) are rare HIV-1-infected patients who exhibit spontaneous viral control. HIC have high frequency of CD38-/HLA-DR+ HIV-specific CD8+ T cells. Here we examined the role of this subset in HIC status.<h4>Materials and methods</h4>We compared CD38-/HLA-DR+ CD8+ T cells with the classical CD38+/HLA-DR+ activated phenotype in terms of 1) their activation status, reflected by CD69, CD25, CD71, CD40 and Ki67 expression, 2) functional parameters: Bcl-2 expression, p  ...[more]

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