RESUMEN
Double negative (DN) T cells are CD3(+), CD4(-), CD8(-) cells with either T-cell receptors (TCR) αß 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 MIP1ß (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/αß(+) and DN/γδ(+) T-cells through MIP1ß 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.
Asunto(s)
VIH/inmunología , Subgrupos de Linfocitos T/inmunología , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/inmunología , Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Adulto , Complejo CD3/análisis , Antígenos CD4/análisis , Antígenos CD8/análisis , Femenino , Humanos , Interferón gamma/biosíntesis , Masculino , Persona de Mediana Edad , Parejas Sexuales , Subgrupos de Linfocitos T/químicaRESUMEN
The mechanism explaining the failure of HIV-specific CD8(+) T cell responses to successfully control HIV replication remains elusive. A total of 83 drug-naive HIV-infected individuals, 27 of whom were long-term nonprogressors (LTNP), was examined. The ability of CD8(+) T lymphocytes to produce three different cytokines (MIP-1beta, TNF-alpha, IL-2) in response to HIV Gag and Nef peptides and to polyclonal stimuli and the ability of HIV-specific CD8(+) T cells to expand in vitro were evaluated by multiparameter flow cytometry. In response to polyclonal stimulation, LTNP presented significantly higher levels of several CD8(+) T cell subsets than progressors. While most patients presented detectable Gag and Nef-specific CD8(+) responses, no significant differences in any of the CD8(+) functional T cell subsets were recognized when comparing LTNP and progressors. HIV responses were dominated by cells producing only MIP-1beta or TNF-alpha, being similar in LTNP and progressors. However, expansion of HIV-specific CD8(+) T cells was more frequent in LTNP than progressors, especially for cells producing MIP-1beta. LTNP show higher levels of CD8(+) responses against polyclonal stimuli than progressors. However, HIV-specific CD8(+) responses do not differ between them except for a more preserved ability of cells from LTNP to expand in vitro.