title: HIV Gag-specific immune response mediated by double negative (CD3(+)CD4(-)CD8(-)) T cells in HIV-exposed seronegative individuals.
abstract: Double negative (DN) T cells are CD3(+), CD4(-), CD8(-) cells with either T-cell receptors (TCR) αβ or TCR γδ whose importance on protection against HIV infection is unknown. Since HIV-exposed seronegative individuals correspond to an ideal group in whom correlates of protection are expected, the role of these cells was studied in 13 HIV-serodiscordant couples in a stable relationship and reporting unprotected sexual intercourses. HIV-specific immune responses mediated by DN T-cells were evaluated by measuring intracellular IFNγ and MIP1β (CCL4) production in response to HIV-Gag peptides. Thirty-five healthy controls not exposed to HIV were tested similarly and used to define a threshold for positive responses. Interestingly, Gag-specific DN T-cell responses were found in 3/13 (23%) HIV-exposed seronegative individuals (Group A), involving both DN/αβ(+) and DN/γδ(+) T-cells through MIP1β and IFNγ production. 4/13 (30%) of partners infected with HIV (Group B) also showed Gag-specific responses but were mediated exclusively by DN/γδ(+) T-cells, mainly through IFNγ production. DN T-cells in Group A individuals can display differential HIV-specific immune responses, which might contribute to the low susceptibility to infection with HIV shown by individuals in Group A.
authors.affiliation: Infectious Diseases Department, Hospital Carlos III, Madrid, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Restrepo
authors.forename: Norma I
authors.initials: NI
authors.lastname: Rallón
authors.forename: Jorge
authors.initials: J
authors.lastname: del Romero
authors.forename: Carmen
authors.initials: C
authors.lastname: Rodríguez
authors.forename: José M
authors.initials: JM
authors.lastname: Sempere-Ortells
authors.forename: Elvira
authors.initials: E
authors.lastname: de la Vega
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
authors.forename: José M
authors.initials: JM
authors.lastname: Benito
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis; D000328:Adult; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D005260:Female; D006678:HIV / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D012747:Sexual Partners; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; C493277:MAPKAP1 protein, human; D054301:gag Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma