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In the present study, we have investigated the distribution of HIV-specific and HIV-infected CD4 T cells within different populations of memory CD4 T cells isolated from lymph nodes of viremic HIV-infected subjects. Four memory CD4 T cell populations were identified on the basis of the expression of CXCR5, PD-1, and Bcl-6: CXCR5⁻PD-1⁻Bcl-6⁻, CXCR5⁺PD-1⁻Bcl-6⁻, CXCR5⁻PD-1⁺Bcl-6⁻, and CXCR5⁺PD-1⁺Bcl-6⁺. On the basis of Bcl-6 expression and functional properties (IL-21 production and B cell help), the CXCR5⁺PD-1⁺Bcl-6⁺ cell population was considered to correspond to the T follicular helper (Tfh) cell population. We show that Tfh and CXCR5⁻PD-1⁺ cell populations are enriched in HIV-specific CD4 T cells, and these populations are significantly increased in viremic HIV-infected subjects as compared with healthy subjects. The Tfh cell population contained the highest percentage of CD4 T cells …