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

doi:10.1038/srep10443

T_FH 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 journal › Article › peer-review

45 Scopus citations

Abstract

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.

Original language	English
Article number	10443
Journal	Scientific Reports
Volume	5
DOIs	https://doi.org/10.1038/srep10443
State	Published - 2 Jun 2015
Externally published	Yes

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@article{a1f3e4b927d54517882b7d98bdcf92ce,

title = "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 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.",

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

note = "Funding Information: The authors thank Doris Thelian for her help with the flow cytometry and data analysis; Mathew Creegan for cell sorting; Michael Eller for flow core facilities; Elaine Morrison for inoculation, bleeding, and mouse husbandry; Agnes-Laurence Chenine for help in obtaining the human tissue and Hendrik Streeck for reading the manuscript and providing critical comments. This work was supported by a cooperative agreement (W81XWH-11-2-0174) between the Henry M. Jackson Foundation and the US Department of Defense. Jiae Kim is supported by a NIAID, NIH (AI102725) grant.",

year = "2015",

month = jun,

day = "2",

doi = "10.1038/srep10443",

language = "English",

volume = "5",

journal = "Scientific Reports",

issn = "2045-2322",

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TY - JOUR

T1 - TFH cells accumulate in mucosal tissues of humanized-DRAG mice and are highly permissive to HIV-1

AU - Allam, Atef

AU - Majji, Sai

AU - Peachman, Kristina

AU - Jagodzinski, Linda

AU - Kim, Jiae

AU - Ratto-Kim, Silvia

AU - Wijayalath, Wathsala

AU - Merbah, Melanie

AU - Kim, Jerome H.

AU - Michael, Nelson L.

AU - Alving, Carl R.

AU - Casares, Sofia

AU - Rao, Mangala

N1 - Funding Information: The authors thank Doris Thelian for her help with the flow cytometry and data analysis; Mathew Creegan for cell sorting; Michael Eller for flow core facilities; Elaine Morrison for inoculation, bleeding, and mouse husbandry; Agnes-Laurence Chenine for help in obtaining the human tissue and Hendrik Streeck for reading the manuscript and providing critical comments. This work was supported by a cooperative agreement (W81XWH-11-2-0174) between the Henry M. Jackson Foundation and the US Department of Defense. Jiae Kim is supported by a NIAID, NIH (AI102725) grant.

PY - 2015/6/2

Y1 - 2015/6/2

N2 - 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.

AB - 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.

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U2 - 10.1038/srep10443

DO - 10.1038/srep10443

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SN - 2045-2322

VL - 5

JO - Scientific Reports

JF - Scientific Reports

M1 - 10443

ER -

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

Abstract

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