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CD4 +  T follicular helper cells (T FH ) in germinal centers are required for maturation of B-cells. While the role of T FH -cells has been studied in blood and lymph nodes of HIV-1 infected individuals, its role in the mucosal tissues has not been investigated. We show that the gut and female reproductive tract (FRT) of humanized DRAG mice have a high level of human lymphocytes and a high frequency of T FH  (CXCR5 + PD-1 ++ ) and precursor-T FH  (CXCR5 + PD-1 + ) cells. The majority of T FH -cells expressed CCR5 and CXCR3 and are the most permissive to HIV-1 infection. A single low-dose intravaginal HIV-1 challenge of humanized DRAG mice results in 100% infectivity with accumulation of T FH -cells mainly in the Peyer’s patches and FRT. The novel finding of T FH -cells in the FRT may contribute to the high susceptibility of DRAG mice to HIV-1 infection. This mouse model thus provides new opportunities to study T FH -cells and to evaluate HIV-1 vaccines.

TFH cells accumulate in mucosal tissues of humanized-DRAG mice and are highly permissive to HIV-1