T follicular regulatory cells (T<inf>FR</inf>) are a suppressive CD4<sup>+</sup> T cell subset that migrates to germinal centers (GC) during Ag presentation by upregulating the chemokine receptor CXCR5. In the GC, T<inf>FR</inf> control T follicular helper cell (T<inf>FH</inf>) expansion andmodulate the development of high-affinity Ag-specific responses. In this study, we identified and characterized T<inf>FR</inf> 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<inf>FR</inf> were infected by SIV<inf>mac251</inf> and had comparable levels of SIV DNA to CXCR5-CCR7+ "T zone" T regulatory cells and T<inf>FH</inf>. Contrary to the SIV-associated T<inf>FH</inf> expansion in the chronic phase of infection, we observed an apparent reduction of T<inf>FR</inf> frequency in cell suspension, as well as a decrease of CD3+Foxp3+ cells in the GC of intact lymph nodes. T<inf>FR</inf> frequency was inversely associated with the percentage of T<inf>FH</inf> and, interestingly, with the avidity of the Abs that recognize the SIV gp120 envelope protein. Our findings show changes in the T<inf>FH</inf>/T<inf>FR</inf> ratio during chronic infection and suggest possible mechanisms for the unchecked expansion of T<inf>FH</inf> cells in HIV/SIV infection.
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