Elevated Numbers of HIV-Specific Poly-Functional CD8+ T Cells With Stem Cell-Like and Follicular Homing Phenotypes in HIV-Exposed Seronegative Individuals

Abstract

HIV-specific CD8+ T cells are known to play a key role in viral control during acute and chronic HIV infection. Although many studies have demonstrated the importance of HIV-specific CD8+ T cells in viral control, its correlation with protection against HIV infection remains incompletely understood. To better understand the nature of the immune response that contributes to the early control of HIV infection, we analyzed the phenotype, distribution and function of anti-viral CD8+ T cells in a cohort of HIV-exposed seronegative (HESN) women, and compared them with healthy controls and HIV-infected individuals. Further, we evaluated the in vitro viral inhibition activity of CD8+ T cells against diverse HIV-1 strains. We found that the HESN group had significantly higher levels of CD8+ T cells that express T-stem cell-like (TSCM) and follicular homing (CXCR5+) phenotype with more effector like characteristics as compared to healthy controls. Further, we observed that the HESN population had a higher frequency of HIV-specific poly-functional CD8+ T cells with robust in vitro virus inhibiting capacity against different clades of HIV. Overall, our results demonstrate that the HESN population has elevated levels of HIV-specific poly-functional CD8+ T cells with robust virus inhibiting ability and express elevated levels of markers pertaining to TSCM and follicular homing phenotype. These results demonstrate that future vaccine and therapeutic strategies should focus on eliciting these critical CD8+ T cell subsets.

WITHDRAWN: Immunogenicity of a cold-chain friendly and long-term stable HIV multi-epitope protease cleavage sites (MEPCS)-mRNA-LNP vaccine.

“…It is a robust predictor of T-cell efficacy in promoting protective immune response 40 . Studies on the HESN population have also revealed that the elevated levels of HIV-specific polyfunctional CD8+ T-cells and associated effector molecules are responsible for robust virus-inhibiting and keeping the plasma viral load undetectable 41 . Thus, we next evaluated the PCS-induced T-cell polyfunctionality, which is based on PCSstimulated T-cell's ability to secrete cytokines.…”

Deciphering the Role of Mucosal Immune Responses and the Cervicovaginal Microbiome in Resistance to HIV Infection in HIV-Exposed Seronegative (HESN) Women

“…We found significantly elevated frequencies of CXCR5 + CD8 T cells and polyfunctional T cells, with stem cell likeness in HESN individuals. In addition, we also demonstrated a potent in vitro viral inhibition activity in the HESN population compared to HIV-infected and HIV-unexposed counterparts ( 60 ). To our knowledge, this is the first study reporting higher frequencies of Tfh and CXCR5 + CD8 + T cells in HESN cohorts from India.…”

T cell immunity to SARS-CoV-2

“…In addition to asymptomatic patients, highly-exposed seronegative individuals show a readily detectable response that is significantly stronger than in healthy and unexposed donors [ 23 , 49 , 50 ]. Polyfunctional T cell responses in highly-exposed seronegative individuals has also been described in the context of HIV [ 51 ], which correlated to people resistant to infections [ 52 ]. Whether this type of T cell responses in the absence of antibodies will be able to protect from SARS-CoV-2 infection or severe disease remain to be determined.…”