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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.

SUBMITTER: Munusamy Ponnan S

PROVIDER: S-EPMC8056154 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Munusamy Ponnan Sivasankaran S Thiruvengadam Kannan K Kathirvel Sujitha S Shankar Janani J Rajaraman Akshaya A Mathaiyan Manikannan M Dinesha Thongadi Ramesh TR Poongulali Selvamuthu S Saravanan Shanmugam S Murugavel Kailapuri Gangatharan KG Swaminathan Soumya S Tripathy Srikanth Prasad SP Neogi Ujjwal U Velu Vijayakumar V Hanna Luke Elizabeth LE

Frontiers in immunology 20210315

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 ...[more]

PMID: 33889151

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Project description:BackgroundDisruption of gastrointestinal tract epithelial and immune barriers contribute to microbial translocation, systemic inflammation, and progression of HIV-1 infection. Antiretroviral therapy (ART) may lead to reconstitution of CD4+ T cells in gut-associated lymphoid tissue (GALT), but its impact on humoral immunity within GALT is unclear. Therefore, we studied CD4+ subsets, including T follicular helper cells (Tfh), as well as resident B cells that have switched to IgA production, in gut biopsies, from HIV+ subjects on suppressive ART compared to HIV-negative controls (HNC).MethodsTwenty-three HIV+ subjects on ART and 22 HNC undergoing colonoscopy were recruited to the study. Single-cell suspensions were prepared from biopsies from left colon (LC), right colon (RC), and terminal ileum (TI). T and B lymphocyte subsets, as well as EpCAM+ epithelial cells, were accurately enumerated by flow cytometry, using counting beads.ResultsNo significant differences in the number of recovered epithelial cells were observed between the two subject groups. However, the median TI CD4+ T cell count/106 epithelial cells was 2.4-fold lower in HIV+ subjects versus HNC (19,679 versus 47,504 cells; p = 0.02). Similarly, median LC CD4+ T cell counts were reduced in HIV+ subjects (8,358 versus 18,577; p = 0.03) but were not reduced in RC. Importantly, we found no significant differences in Tfh or IgA+ B cell counts at either site between HIV+ subjects and HNC. Further analysis showed no difference in CD4+, Tfh, or IgA+ B cell counts between subjects who commenced ART in primary compared to chronic HIV-1 infection. Despite the decrease in total CD4 T cells, we could not identify a selective decrease of other key subsets of CD4+ T cells, including CCR5+ cells, CD127+ long-term memory cells, CD103+ tissue-resident cells, or CD161+ cells (surrogate marker for Th17), but there was a slight increase in the proportion of T regulatory cells.ConclusionWhile there were lower absolute CD4+ counts in the TI and LC in HIV+ subjects on ART, they were not associated with significantly reduced Tfh cell counts or IgA+ B cells, suggesting that this important vanguard of adaptive immune defense against luminal microbial products is normalized following ART.

Dataset Information

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

Publications

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

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