Regulatory and Helper Follicular T Cells and Antibody Avidity to Simian Immunodeficiency Virus Glycoprotein 120

T follicular regulatory cells (T-FR) are a suppressive CD4(+) T cell subset that migrates to germinal centers (GC) during Ag presentation by upregulating the chemokine receptor CXCR5. In the GC, T-FR control T follicular helper cell (T-FH) expansion andmodulate the development of high-affinity Ag-specific responses. In this study, we identified and characterized T-FR as CXCR5(+) CCR7(-) "follicular" T regulatory cells in lymphoid tissues of healthy rhesus macaques, and we studied their dynamics throughout infection in a welldefined animal model of HIV pathogenesis. T-FR were infected by SIVmac251 and had comparable levels of SIV DNA to CXCR5(-) CCR7(+) "T zone" T regulatory cells and T-FH. Contrary to the SIV-associated T-FH expansion in the chronic phase of infection, we observed an apparent reduction of T-FR frequency in cell suspension, as well as a decrease of CD3(+)Foxp3(+) cells in the GC of intact lymph nodes. T-FR frequency was inversely associated with the percentage of T-FH and, interestingly, with the avidity of the Abs that recognize the SIV gp120 envelope protein. Our findings show changes in the T-FH/T-FR ratio during chronic infection and suggest possible mechanisms for the unchecked expansion of T-FH cells in HIV/SIV infection.