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.
authors.affiliation: 1] US Military HIV Research Program, Walter Reed Army Institute of Research [2] Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
authors.forename: Atef
authors.initials: A
authors.lastname: Allam
authors.affiliation: US Military Malaria Vaccine Program, Naval Medical Research Center, Silver Spring, Maryland, USA.
authors.forename: Sai
authors.initials: S
authors.lastname: Majji
authors.affiliation: 1] US Military HIV Research Program, Walter Reed Army Institute of Research [2] Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Peachman
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research.
authors.forename: Linda
authors.initials: L
authors.lastname: Jagodzinski
authors.affiliation: 1] US Military HIV Research Program, Walter Reed Army Institute of Research [2] Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
authors.forename: Jiae
authors.initials: J
authors.lastname: Kim
authors.affiliation: 1] US Military HIV Research Program, Walter Reed Army Institute of Research [2] Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ratto-Kim
authors.affiliation: US Military Malaria Vaccine Program, Naval Medical Research Center, Silver Spring, Maryland, USA.
authors.forename: Wathsala
authors.initials: W
authors.lastname: Wijayalath
authors.affiliation: 1] US Military HIV Research Program, Walter Reed Army Institute of Research [2] Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Merbah
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research.
authors.forename: Carl R
authors.initials: CR
authors.lastname: Alving
authors.affiliation: US Military Malaria Vaccine Program, Naval Medical Research Center, Silver Spring, Maryland, USA.
authors.forename: Sofia
authors.initials: S
authors.lastname: Casares
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research.
authors.forename: Mangala
authors.initials: M
authors.lastname: Rao
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D060889:Inducible T-Cell Co-Stimulator Protein / Q000378:metabolism; D007378:Interleukins / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000276:immunology* / Q000378:metabolism; D010581:Peyer's Patches / Q000276:immunology / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D000098546:Interleukin-21
chemical_list: D000954:Antigens, Surface; D060889:Inducible T-Cell Co-Stimulator Protein; D007378:Interleukins; D051560:Proto-Oncogene Proteins c-bcl-6; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D017493:Leukocyte Common Antigens; D000098546:Interleukin-21