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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Antigens, Surface / metabolism
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B-Lymphocyte Subsets / immunology
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B-Lymphocyte Subsets / metabolism
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Disease Models, Animal
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Disease Susceptibility
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Female
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HIV Infections / immunology*
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HIV Infections / virology*
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HIV-1 / immunology*
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Humans
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Immunophenotyping
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Inducible T-Cell Co-Stimulator Protein / metabolism
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Interleukins / biosynthesis
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Leukocyte Common Antigens / metabolism
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Lymphoid Tissue / immunology
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Lymphoid Tissue / metabolism
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Mice
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Mice, Transgenic
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Mucous Membrane / immunology*
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Mucous Membrane / metabolism
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Peyer's Patches / immunology
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Peyer's Patches / metabolism
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Proto-Oncogene Proteins c-bcl-6 / metabolism
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Receptors, CCR5 / metabolism
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Receptors, CXCR3 / metabolism
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / virology
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T-Lymphocytes, Helper-Inducer / immunology*
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T-Lymphocytes, Helper-Inducer / metabolism
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T-Lymphocytes, Helper-Inducer / virology*
Substances
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Antigens, Surface
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Inducible T-Cell Co-Stimulator Protein
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Interleukins
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Proto-Oncogene Proteins c-bcl-6
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Receptors, CCR5
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Receptors, CXCR3
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Leukocyte Common Antigens
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interleukin-21