title: Imbalanced production of cytokines by T cells associates with the activation/exhaustion status of memory T cells in chronic HIV type 1 infection.
abstract: Chronic HIV-1 infection is characterized by immune cell dysfunctions driven by chronic immune activation. Plasma HIV-1 viral load (VL) is closely correlated with disease progression and the level of immune activation. However, the mechanism by which the persistent presence of HIV-1 damages immune cells is still not fully understood. To evaluate how HIV-1 affects disruption of T cell-mediated immune responses during chronic HIV-1 infection we determined the functional profiles of T cells from subjects with chronic HIV-1 infection. We measured the capacity of peripheral blood mononuclear cells (PBMCs) to produce 25 specific cytokines in response to nonspecific T cell stimulation, and found that the capacity to produce Th-1-related cytokines (MIP-1α, MIP-1β, RANTES, IFN-γ, and MIG), sIL-2R, and IL-17, but not Th-2-related cytokines, was inversely correlated with plasma VL. The capacities to produce these cytokines were interrelated; notably, IL-17 production had a strong direct correlation with production of MIP-1α, MIP-1β, RANTES, and IFN-γ. In both CD4(+) and CD8(+) T cells, dysfunctional production of cytokines was associated with T cell activation (CD38 expression) and exhaustion (PD-1 and/or CTLA-4 expression) status of memory subsets. Although the capacity to produce these cytokines was recovered soon after multiple log(10) reduction of plasma viral levels by antiretroviral therapy, memory CD8(+) T cells remained activated and exhausted after prolonged virus suppression. Our data suggest that HIV-1 levels directly affect the ability of memory T cells to produce specifically Th1- and Th17-related cytokines during chronic HIV-1 infection.
authors: Division of Infectious Diseases, Advanced Clinical Research Center, The University of Tokyo, Tokyo, Japan.
authors: Kaori
authors: K
authors: Nakayama
authors: Hitomi
authors: H
authors: Nakamura
authors: Michiko
authors: M
authors: Koga
authors: Tomohiko
authors: T
authors: Koibuchi
authors: Takeshi
authors: T
authors: Fujii
authors: Toshiyuki
authors: T
authors: Miura
authors: Aikichi
authors: A
authors: Iwamoto
authors: Ai
authors: A
authors: Kawana-Tachikawa
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006679:HIV Seropositivity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D008213:Lymphocyte Activation; D019402:Macrophage Inflammatory Proteins / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load; D055815:Young Adult
chemical_list: D016207:Cytokines; D019402:Macrophage Inflammatory Proteins