2015
DOI: 10.1038/srep10443
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TFH cells accumulate in mucosal tissues of humanized-DRAG mice and are highly permissive to HIV-1

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 ar… Show more

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Cited by 46 publications
(52 citation statements)
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References 71 publications
(105 reference statements)
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“…Moreover, the data presented here demonstrate a marked expansion of these CXCR3 + GC-Tfh cells during SIV infection. Similar findings were reported in the blood of HIV infected individuals as well as mouse model of HIV infection where CXCR3 + CD4 T cells preferentially expressed the HIV-co-receptor CCR5 (45, 51). Hence, we speculate that CXCR3 + CCR5 + α4β7 + GC-Tfh subsets may have the capacity to maintain a dynamic viral reservoir in GCs under anti-retroviral therapy.…”
Section: Discussionsupporting
confidence: 84%
“…Moreover, the data presented here demonstrate a marked expansion of these CXCR3 + GC-Tfh cells during SIV infection. Similar findings were reported in the blood of HIV infected individuals as well as mouse model of HIV infection where CXCR3 + CD4 T cells preferentially expressed the HIV-co-receptor CCR5 (45, 51). Hence, we speculate that CXCR3 + CCR5 + α4β7 + GC-Tfh subsets may have the capacity to maintain a dynamic viral reservoir in GCs under anti-retroviral therapy.…”
Section: Discussionsupporting
confidence: 84%
“…It is also possible that infected T h 17 cells directly become T fh cells (32,33), which would then be capable of migration to secondary lymphoid tissues (Fig. 7), where they are capable of replication at high levels, despite their low expression of CCR5 (68,69). Our findings may aid in therapeutic intervention strategies aimed at preventing viral production during acute HIV infection or reducing the size of the viral reservoir in people living with HIV.…”
Section: Discussionmentioning
confidence: 94%
“…The heightened permissivity of tonsillar T FH cannot be fully explained by differences in memory subsets, cellular activation, or chemokine co-receptor expression [9]. Importantly, in an HIV-model system using humanized mice, T FH rapidly accumulate in gut and female reproductive tract mucosal tissues and are the most permissive CD4+ T cell subset to HIV [10], suggesting that gut and vaginal T FH may play a key role in establishment of HIV infection as well as ongoing virus replication.…”
Section: Role Of Tfh In Hiv Replication In Untreated Diseasementioning
confidence: 99%