title: Evolution of the functional profile of HIV-specific CD8+ T cells in patients with different progression of HIV infection over 4 years.
abstract: There is a lack of information about the stability of these responses over time in subjects experiencing differences in HIV disease progression. The functional profile of Gag-specific and Nef-specific CD8T-cell responses based on the simultaneous production macrophage inflammatory protein (MIP)-1beta, interleukin (IL)-2, and tumor necrosis factor (TNF)-alpha was longitudinally assessed using flow cytometry over 4 years in 8 elite controllers (EC), 8 viremic controllers, 10 antiretroviral-naive typical progressors, and 10 patients with virological suppression (VS) on antiretroviral therapy. CD8 T-cell subsets with 2 functions tended to decline, whereas subsets with 1 function tended to increase over time in typical progressors. In viremic controller, Gag and Nef responses evolved differently. In EC, the functional profile of Gag-specific CD8T-cell responses evolved increasing polyfunctionality over time. Finally, Nef-specific responses in VS increased in the MIP+TNF-IL2- CD8 T-cell subset while Gag-specific responses did not change. The functional profile of HIV-specific CD8T-cell responses may evolve in different ways depending of the targeted HIV protein and the ability to control virus replication. In patients with uncontrolled HIV replication, the functionality of Gag-specific CD8T-cell responses tends to diminish over time, whereas in EC, there is an increase in polyfunctional subsets. Interestingly, VS do not seem to restore the polyfunctional profile of HIV-specific CD8T-cell responses.
authors.affiliation: Molecular Biology Laboratory, Service of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Peris-Pertusa
authors.forename: Mariola
authors.initials: M
authors.lastname: López
authors.forename: Norma I
authors.initials: NI
authors.lastname: Rallón
authors.forename: Clara
authors.initials: C
authors.lastname: Restrepo
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
authors.forename: José M
authors.initials: JM
authors.lastname: Benito
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D054407:Chemokine CCL4 / Q000096:biosynthesis; D018450:Disease Progression; D005434:Flow Cytometry; D015683:Gene Products, gag / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008137:Longitudinal Studies; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: C066507:CCL4 protein, human; D054407:Chemokine CCL4; D015683:Gene Products, gag; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D054311:nef Gene Products, Human Immunodeficiency Virus