CD8⁺ T cell responses to human immunodeficiency viruses type 2 (HIV‐2) and type 1 (HIV‐1) gag proteins are distinguishable by magnitude and breadth but not cellular phenotype

Abstract

The mechanisms underlying the relatively slow progression of human immunodeficiency virus type 2 (HIV‐2) compared with HIV‐1 infection are undefined and could be a result of more effective immune responses. We used HIV‐2 and HIV‐1 IFN‐γ enzyme‐linked immunospot assays to evaluate CD8+ T cell responses in antiretroviral‐naive HIV‐2‐ (‘HIV‐2+’) and HIV‐1‐infected (‘HIV‐1+’) individuals. Gag‐specific responses were detected in the majority of HIV‐2+ and HIV‐1+ subjects. Overlapping gag peptide analysis indicated a significantly greater magnitude and breadth of responses in the HIV‐1+ cohort, and this difference was attributable to low responses in HIV‐2+ subjects with undetectable viral load (medians 2107 and 512 spot‐forming units per 106 PBMC, respectively, p=0.007). We investigated the phenotype of viral epitope‐specific CD8+ T cells identified with HLA‐B53‐ and HLA‐B58‐peptide tetramers (8 HIV‐2+, 11 HIV‐1+ subjects). HIV‐2‐specific CD8+ T cells were predominantly CD27+ CD45RA–, and only a minority expressed perforin. The limited breadth and low frequency of CD8+ T cell responses to HIV‐2 gag in aviremic HIV‐2+ subjects suggests that these responses reflect antigen load in plasma, as is the case in HIV‐1 infection. Immune control of HIV‐2 does not appear to be related to the frequency of perforin‐expressing virus‐specific CD8+ T cells.

Polyfunctional T cell responses are a hallmark of HIV‐2 infection

“…HIV-2-specific CD8 + T cell responses have been shown to be present [9,10], but not different from HIV-1-specific responses in terms of IFN-c production [11][12][13], proliferative capacity [14], or cytotoxicity [12], suggesting that these aspects of the adaptive immune response to HIV-2 are not defining features contributing to enhanced viral control and better clinical outcome. As has been reported previously in other virusspecific CD8 + T cell responses [23,24], we found that MIP-1b was even more prominent than IFN-c in the HIVspecific CD8 + T cell response, in both HIV-1 and HIV-2 infected individuals.…”

“…HIV-2-specific CD8 + T cell immune responses have been shown to be present [9,10], but not different from HIV-1-specific responses in terms of IFN-c production [11][12][13], proliferative capacity [14], or cytotoxicity [12], suggesting that these aspects of the adaptive immune response to HIV-2 are not the key features contributing to enhanced viral control and better clinical outcome. One of the characteristic immune defects in HIV-1 infection is the early loss of HIV-specific CD4 + T cells that have proliferative capacity and the ability to secrete IL-2 [15,16].…”

Robust Gag-specific T cell responses characterize viremia control in HIV-2 infection

“…However, the contribution of the cellular immune system to viremia control is controversial, with evidence to support either a positive (18,19), a negative (14,(24)(25)(26), or no correlation (17,21,22) with HIV-1 plasma viral load (VL). Previous studies in HIV-2 infection similarly report positive (27), negative (10,11,28), or no correlation (29,30) with clinical markers of disease progression. However, past investigations of HIV-2-specific immune responses have been constrained by incomplete coverage of the entire HIV-2 proteome, and until now, there has been no comprehensive study of antigen-specific immune responses directed against the HIV-2-expressed genome.…”

“…Since there is no information on HIV-2 specific immune responses to the entire HIV-2 expressed genome, we derived the expected number of positive peptides based on data from HIV-1-specific IFN-γ responses that suggest that approximately 18 epitopic regions are recognized (17). Past data show that the mean magnitude of responses to homologous HIV-1 and HIV-2 Gag, Tat, and Env gene products is either similar (29) or lower when compared with HIV-1-specific responses (27). Therefore, recognition of 18 or less epitopic regions would be expected per HIV-2-positive subject.…”

Gag-Specific CD4+T-Cell Frequency Is Inversely Correlated with Proviral Load and Directly Correlated with Immune Activation in Infection with Human Immunodeficiency Virus Type 2 (HIV-2) but Not HIV-1

“…Although no major differences in the frequencies of HIVspecific CD8 ϩ T cells have been reported in HIV-1-and HIV-2-infected individuals (2,4,8,9,13,15), HIV-2-specific CD8 ϩ T cells have been shown to recognize a broader range of viral proteins (30) and to have a higher functional flexibility (16). HIV-2-specific CD4 ϩ T cells have been less well characterized (6,7,21,22,30), though a better preserved proliferative capacity has been shown (6).…”