Several studies have demonstrated the significance of antiviral CD8 + T cells in the control of HIV infection. The hallmark of the adaptive immune response is the generation of long-lived immunological memory following exposure to an antigen ( 7). In order to make progress toward achieving sustained viral remission, complementary approaches that can reduce latent HIV-1 reservoirs and enhance anti-HIV immunity in drug-treated individuals are needed ( 6). However, infected individuals need to be on ART for the rest of their life due to persisting viral reservoirs in the body ( 2– 5) that lead to rapid viral rebound following treatment interruption. Antiretroviral therapy (ART) is very effective at suppressing HIV replication and prolonging infected individuals' lives by reducing viral load to undetectable levels in the plasma. The World Health Organization (WHO) estimates that there are currently about 33 million people living with the human immunodeficiency virus (HIV) ( 1). These results demonstrate that future vaccine and therapeutic strategies should focus on eliciting these critical CD8 + T cell subsets. 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. 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. 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 evaluated the in vitro viral inhibition activity of CD8 + T cells against diverse HIV-1 strains. 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. 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. HIV-specific CD8 + T cells are known to play a key role in viral control during acute and chronic HIV infection. 7Department of Pathology and Laboratory Medicine, Emory School of Medicine, Emory University, Atlanta, GA, United States.6Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States.5Division of Clinical Microbiology, Karolinska Institute, Stockholm, Sweden.4Chennai Antiviral Research and Treatment Centre and Clinical Research Site (CART CRS), Infectious Diseases Medical Center, Voluntary Health Services (VHS), Chennai, India.Gaitonde (YRG) Center for AIDS Research and Education, Chennai, India
2Centre for Infectious Disease Research, Indian Institute of Science (IISc), Bangalore, India.1National Institute for Research in Tuberculosis (Indian Council of Medical Research), Chennai, India.Sivasankaran Munusamy Ponnan 1,2, Kannan Thiruvengadam 1, Sujitha Kathirvel 1, Janani Shankar 1, Akshaya Rajaraman 1, Manikannan Mathaiyan 1, Thongadi Ramesh Dinesha 3, Selvamuthu Poongulali 4, Shanmugam Saravanan 3, Kailapuri Gangatharan Murugavel 3, Soumya Swaminathan 1, Srikanth Prasad Tripathy 1, Ujjwal Neogi 5, Vijayakumar Velu 6,7 and Luke Elizabeth Hanna 1 * †
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