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

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....

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Main Authors: Sivasankaran Munusamy Ponnan, Kannan Thiruvengadam, Sujitha Kathirvel, Janani Shankar, Akshaya Rajaraman, Manikannan Mathaiyan, Thongadi Ramesh Dinesha, Selvamuthu Poongulali, Shanmugam Saravanan, Kailapuri Gangatharan Murugavel, Soumya Swaminathan, Srikanth Prasad Tripathy, Ujjwal Neogi, Vijayakumar Velu, Luke Elizabeth Hanna
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-03-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2021.638144/full
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author Sivasankaran Munusamy Ponnan
Sivasankaran Munusamy Ponnan
Kannan Thiruvengadam
Sujitha Kathirvel
Janani Shankar
Akshaya Rajaraman
Manikannan Mathaiyan
Thongadi Ramesh Dinesha
Selvamuthu Poongulali
Shanmugam Saravanan
Kailapuri Gangatharan Murugavel
Soumya Swaminathan
Srikanth Prasad Tripathy
Ujjwal Neogi
Vijayakumar Velu
Vijayakumar Velu
Luke Elizabeth Hanna
author_facet Sivasankaran Munusamy Ponnan
Sivasankaran Munusamy Ponnan
Kannan Thiruvengadam
Sujitha Kathirvel
Janani Shankar
Akshaya Rajaraman
Manikannan Mathaiyan
Thongadi Ramesh Dinesha
Selvamuthu Poongulali
Shanmugam Saravanan
Kailapuri Gangatharan Murugavel
Soumya Swaminathan
Srikanth Prasad Tripathy
Ujjwal Neogi
Vijayakumar Velu
Vijayakumar Velu
Luke Elizabeth Hanna
author_sort Sivasankaran Munusamy Ponnan
collection DOAJ
description 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.
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spelling doaj.art-0d2a5bee558a41c4a2d8f89e7f3c4dc42022-12-21T19:06:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-03-011210.3389/fimmu.2021.638144638144Elevated Numbers of HIV-Specific Poly-Functional CD8+ T Cells With Stem Cell-Like and Follicular Homing Phenotypes in HIV-Exposed Seronegative IndividualsSivasankaran Munusamy Ponnan0Sivasankaran Munusamy Ponnan1Kannan Thiruvengadam2Sujitha Kathirvel3Janani Shankar4Akshaya Rajaraman5Manikannan Mathaiyan6Thongadi Ramesh Dinesha7Selvamuthu Poongulali8Shanmugam Saravanan9Kailapuri Gangatharan Murugavel10Soumya Swaminathan11Srikanth Prasad Tripathy12Ujjwal Neogi13Vijayakumar Velu14Vijayakumar Velu15Luke Elizabeth Hanna16National Institute for Research in Tuberculosis (Indian Council of Medical Research), Chennai, IndiaCentre for Infectious Disease Research, Indian Institute of Science (IISc), Bangalore, IndiaNational Institute for Research in Tuberculosis (Indian Council of Medical Research), Chennai, IndiaNational Institute for Research in Tuberculosis (Indian Council of Medical Research), Chennai, IndiaNational Institute for Research in Tuberculosis (Indian Council of Medical Research), Chennai, IndiaNational Institute for Research in Tuberculosis (Indian Council of Medical Research), Chennai, IndiaNational Institute for Research in Tuberculosis (Indian Council of Medical Research), Chennai, IndiaY. R. Gaitonde (YRG) Center for AIDS Research and Education, Chennai, IndiaChennai Antiviral Research and Treatment Centre and Clinical Research Site (CART CRS), Infectious Diseases Medical Center, Voluntary Health Services (VHS), Chennai, IndiaY. R. Gaitonde (YRG) Center for AIDS Research and Education, Chennai, IndiaY. R. Gaitonde (YRG) Center for AIDS Research and Education, Chennai, IndiaNational Institute for Research in Tuberculosis (Indian Council of Medical Research), Chennai, IndiaNational Institute for Research in Tuberculosis (Indian Council of Medical Research), Chennai, IndiaDivision of Clinical Microbiology, Karolinska Institute, Stockholm, SwedenDivision of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United StatesDepartment of Pathology and Laboratory Medicine, Emory School of Medicine, Emory University, Atlanta, GA, United StatesNational Institute for Research in Tuberculosis (Indian Council of Medical Research), Chennai, IndiaHIV-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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.638144/fullHIVHESNARTCTLCXCR5+ CD8+TSCM cells
spellingShingle Sivasankaran Munusamy Ponnan
Sivasankaran Munusamy Ponnan
Kannan Thiruvengadam
Sujitha Kathirvel
Janani Shankar
Akshaya Rajaraman
Manikannan Mathaiyan
Thongadi Ramesh Dinesha
Selvamuthu Poongulali
Shanmugam Saravanan
Kailapuri Gangatharan Murugavel
Soumya Swaminathan
Srikanth Prasad Tripathy
Ujjwal Neogi
Vijayakumar Velu
Vijayakumar Velu
Luke Elizabeth Hanna
Elevated Numbers of HIV-Specific Poly-Functional CD8+ T Cells With Stem Cell-Like and Follicular Homing Phenotypes in HIV-Exposed Seronegative Individuals
Frontiers in Immunology
HIV
HESN
ART
CTL
CXCR5+ CD8+
TSCM cells
title Elevated Numbers of HIV-Specific Poly-Functional CD8+ T Cells With Stem Cell-Like and Follicular Homing Phenotypes in HIV-Exposed Seronegative Individuals
title_full Elevated Numbers of HIV-Specific Poly-Functional CD8+ T Cells With Stem Cell-Like and Follicular Homing Phenotypes in HIV-Exposed Seronegative Individuals
title_fullStr Elevated Numbers of HIV-Specific Poly-Functional CD8+ T Cells With Stem Cell-Like and Follicular Homing Phenotypes in HIV-Exposed Seronegative Individuals
title_full_unstemmed Elevated Numbers of HIV-Specific Poly-Functional CD8+ T Cells With Stem Cell-Like and Follicular Homing Phenotypes in HIV-Exposed Seronegative Individuals
title_short Elevated Numbers of HIV-Specific Poly-Functional CD8+ T Cells With Stem Cell-Like and Follicular Homing Phenotypes in HIV-Exposed Seronegative Individuals
title_sort elevated numbers of hiv specific poly functional cd8 t cells with stem cell like and follicular homing phenotypes in hiv exposed seronegative individuals
topic HIV
HESN
ART
CTL
CXCR5+ CD8+
TSCM cells
url https://www.frontiersin.org/articles/10.3389/fimmu.2021.638144/full
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