Evaluation of T lymphocytes in HIV-2 infection in West Africa: The role of antigen-specific immune responses in disease non-progression

Both HIV-1 and HIV-2 can cause the Acquired Immunodeficiency Syndrome (AIDS), yet the majority of patients infected with HIV-2 are clinically well and most never experience detrimental effects from the infection. Lessons learned from role of the immune system in the long-term non-progression characteristic of HIV-2 infection could offer insight into how a balanced immune response can protect from the immune system destruction associated with HIV-1 infection. The studies presented in this thesis were carried out in a community-based cohort of HIV-2 long-term non-progressors (LTNPs) in rural Guinea Bissau. The initial work (Chapter 3) outlines the first comprehensive analysis of HIV-2-specific immune responses. The data identified Gag as the most immunogenic HIV-2 protein. The magnitude of interferon gamma (IFN-y) generated against Gag was inversely related to virus load (VL). The most frequently recognised HIV-2 peptides clustered within a defined region of Gag with responses to a si~gle peptide associated with low VL. Given this information, the delineation of HIV-2-specific immune responses was focused on this immunodominant region of the HIV-2 proteome. Included in the detailed analysis was the identification of novel HIV-2 epitopes and ex vivo characterisation of HIV-2-specific T cell function (Chapter 4), in vitro characterisation of HIV-2-specific COB T cell clones (Chapter 5), as well as ex vivo phenotypic analysis of HIV-2-specific COB T cells (Chapter 6). Systemic immune activation is a hallmark of disease progression in both HIV-1 and HIV-2 infection. The final chapter (Chapter 7) examines the contribution of HIV-2 plasma antigenaemia to immune system activation which to date was incompletely defined. Cellular and plasma markers of immune activation were related to clinical (VL and CD4 T cell counts), immunological (HIV-2-specific IFN-y secretion) and virus sequence (p26 phenotype) correlates of protection from progression to AIDS. The aim of this work was to understand better what aspects of the host immune response in chronic HIV-2 infection contribute to the relative maintenance of the immune system during the course of this infection.EThOS - Electronic Theses Online ServiceGBUnited Kingdo