title: HIV rebound after discontinuation of antiretroviral therapy increases and expands HIV-specific CD8+ responses but has no impact on its functionality.
abstract: A higher functionality of CD8(+) T cells might contribute to low-level HIV replication in long-term nonprogressors (LTNPs). However, the contrary could also be true, being the function of CD8(+) T cells modulated by HIV replication. We tested whether enhanced HIV replication following antiretroviral therapy interruption could modify the functional profile of HIV-specific CD8(+) responses. Production of MIP-1beta, IL-2, TNF-alpha, and CD107 expression by CD8(+) T cells in response to Gag and Nef optimal peptide pools was analyzed using polychromatic flow cytometry in nine HIV-infected individuals followed for 12 months after discontinuation of antiretroviral therapy. At baseline, CD8(+) T cell subsets with the greatest contribution to response were MIP-beta(+)TNF-alpha(-)IL-2(-)CD107(+) and MIP-beta(+)TNF-alpha(-)IL-2(-)CD107. Most responses were mediated by subsets expressing only one or two molecules. After 12 months of discontinuing antiretroviral therapy, no significant differences were observed in the functional profile of Gag- and Nef-specific CD8(+) responses. However, viral rebound induced a significant increase in the heterogeneity of Gag-specific CD8(+) responses. In summary, viral replication following discontinuation of antiretroviral therapy has no significant impact on qualitative aspects of HIV-specific CD8(+) responses. Thus, a higher functionality of CD8(+) responses does not seem to be the consequence of low-level virus replication.
authors.affiliation: Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
authors.forename: Mariola
authors.initials: M
authors.lastname: López
authors.forename: Norma
authors.initials: N
authors.lastname: Rallón
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
authors.forename: Isabel
authors.initials: I
authors.lastname: Rodríguez
authors.forename: Eulalia
authors.initials: E
authors.lastname: Valencia
authors.forename: Pablo
authors.initials: P
authors.lastname: Labarga
authors.forename: Victoria
authors.initials: V
authors.lastname: Moreno
authors.forename: Eugenia
authors.initials: E
authors.lastname: Vispo
authors.forename: Fernando
authors.initials: F
authors.lastname: Roncal
authors.forename: Juan
authors.initials: J
authors.lastname: González-Lahoz
authors.forename: José M
authors.initials: JM
authors.lastname: Benito
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D054407:Chemokine CCL4 / Q000096:biosynthesis; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008137:Longitudinal Studies; D052118:Lysosomal-Associated Membrane Protein 1 / Q000096:biosynthesis; D052119:Lysosomal-Associated Membrane Protein 2 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D019562:Viral Load; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: C066507:CCL4 protein, human; D054407:Chemokine CCL4; D007376:Interleukin-2; D052118:Lysosomal-Associated Membrane Protein 1; D052119:Lysosomal-Associated Membrane Protein 2; D014409:Tumor Necrosis Factor-alpha; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus