Follicular Regulatory T Cells and Follicular Helper T Cells: Role in HIV Pathogenesis
The role and function of human T follicular regulatory (TFR) cells in healthy individuals are not completely understood, partly due to its previous grouping with T follicular helper (TFH) cells and partly due to the difficulty in obtaining human secondary lymphoid tissues. A majority of the studies of these two T cell subsets have been done in mice. Up to date, there are only a few studies of human TFR cells in HIV infection in the lymph nodes and the spleen, and peripheral blood TFR cells have not been well defined. The understanding of TFR cells and its phenotypic difference from TFH cells are crucial in the understanding of the humoral response against HIV and other diseases. Also, elucidating TFR cells’ contribution to HIV persistence is important in the path of finding a functional cure for HIV infection. In this Master Thesis, I have examined TFH and TFR cells and their surface markers in human peripheral blood. In Chapter 2 (“Characterization of T Follicular Helper Cells and T Follicular Regulatory Cells in HIV-Infected and non-Infected Individuals”), I investigated the phenotypic characteristics of peripheral blood TFH (pTFR) and TFH (pTFH) cells in peripheral blood mononuclear cells (PBMC) of HIV-infected and HIV non-infected individuals from the Multicenter AIDS Cohort Study (MACS). pTFR cells uniquely expressed the natural T regulatory canonical marker, forkhead box P3 (FOXP3), while pTFH uniquely expressed the TFH cells’ master regulatory, B cell lymphoma 6 (BCL6). An effective way to identify pTFH and pTFR in PBMC only using their surface markers would allow for further functional studies. Collectively, this thesis should further advance the field of basic research of T cells and the field of HIV reservoir, bringing the field closer to a functional cure of HIV Infection.