HIV Gag-specific immune response mediated by double negative (CD3(+)CD4(-)CD8(-)) T cells in HIV-exposed seronegative individuals

• Published in: Journal of medical virology 2013-02, Vol.85 (2), p.200-209
• Main Authors: Restrepo, Clara, Rallón, Norma I, del Romero, Jorge, Rodríguez, Carmen, Sempere-Ortells, José M, de la Vega, Elvira, Soriano, Vincent, Benito, José M
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - biosynthesis; Adult; CD3 Complex - analysis; CD4 Antigens - analysis; CD8 Antigens - analysis; Female; gag Gene Products, Human Immunodeficiency Virus - immunology; HIV - immunology; Humans; Interferon-gamma - biosynthesis; Male; Middle Aged; Sexual Partners; T-Lymphocyte Subsets - chemistry; T-Lymphocyte Subsets - immunology
• ISSN: 1096-9071
• DOI: 10.1002/jmv.23447

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.