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Potential Role for HIV-Specific CD38−/HLA-DR+ CD8+ T Cells in Viral Suppression and Cytotoxicity in HIV Controllers
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Potential Role for HIV-Specific CD38−/HLA-DR+ CD8+ T Cells in Viral Suppression and Cytotoxicity in HIV Controllers
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Journal Article
Potential Role for HIV-Specific CD38−/HLA-DR+ CD8+ T Cells in Viral Suppression and Cytotoxicity in HIV Controllers
2014
Overview
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.
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.
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.
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.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
Acquired immune deficiency syndrome
/ ADP-ribosyl Cyclase 1 - immunology
/ Adult
/ AIDS
/ Antigens
/ CD8-Positive T-Lymphocytes - immunology
/ Female
/ Histocompatibility antigen HLA
/ HIV
/ HIV Infections - prevention & control
/ HLA-DR Antigens - immunology
/ Human immunodeficiency virus
/ Humans
/ Male
/ Medicine and health sciences
/ Peptides
/ T-Lymphocytes, Cytotoxic - immunology
/ Toxicity
