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

Atef Allam*, Sai Majji, Kristina Peachman, Linda Jagodzinski, Jiae Kim, Silvia Ratto-Kim, Wathsala Wijayalath, Melanie Merbah, Jerome H. Kim, Nelson L. Michael, Carl R. Alving, Sofia Casares, Mangala Rao

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

CD4+ T follicular helper cells (TFH) in germinal centers are required for maturation of B-cells. While the role of TFH-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 TFH (CXCR5+PD-1++) and precursor-TFH (CXCR5+PD-1+) cells. The majority of TFH-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 TFH-cells mainly in the Peyer's patches and FRT. The novel finding of TFH-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 TFH-cells and to evaluate HIV-1 vaccines.

Original languageEnglish
Article number10443
JournalScientific Reports
Volume5
DOIs
StatePublished - 2 Jun 2015
Externally publishedYes

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