HIV-1 Infection Impairs HSV-Specific CD4+ and CD8+ T-Cell Response by Reducing Th1 Cytokines and CCR5 Ligand Secretion

Background: The concept of HIV-1/HSV-negative immunosynergy has recently come to light, which leads us to explore the impact of HIV-1 infection on HSV-specific T-cell immunity. Methods: A combination of interferon (IFN)-gamma ELISpot and Luminex-based multicytokine profiling assays was used to compare, in a cross-sectional study, the HSV-specific CD4(+) and CD8(+) T-cell responses between 20 HIV-1/HSV-coinfected and 12 HIV-1-uninfected/HSV-infected individuals after in vitro restimulation with HSV glycoprotein D (gD) peptide epitopes. Results: In response to CD4(+) and CD8(+) gD peptide epitopes, mean value (+/- standard errors of the mean) of the different IFN-gamma-secreting T cells (ISC) means was significantly reduced in HIV-1/HSV-coinfected individuals (70 ISC +/- 10 and 60 ISC +/- 8/10(6) cells) compared with HIV-1-uninfected/HSV-infected individuals (280 ISC +/- 25 and 234 ISC +/- 23/10(6) cells, both P < 0.001). After stimulation with the immunodominant CD4(+) gD(228-258) and CD8(+) gD(53-61) peptide epitopes, the Th1 cytokine and CCR5 ligand secretions were decreased in the HIV-1-infected group although Th17 cytokines increased. The mean concentration of interleukin (IL)-2, IFN-gamma, the IFN-gamma-induced protein 10 kDa, and the monokine induced by IFN-gamma was correlated to the mean concentration of macrophage inflammatory proteins (MIP-1 alpha, MIP-1 beta), RANTES and Eotaxin (rho = 0.56, P = 0.02 and rho = 0.52, P = 0.03). Conclusions: HIV-1 infection impairs both the number and function of HSV-specific T cells. The downregulation of Th1 cytokines and CCR5 ligands in HIV-1/HSV-coinfected individuals may further facilitate both HSV reactivations and HIV-1 replication.