title: Lymphocyte activation gene-3 expression defines a discrete subset of HIV-specific CD8+ T cells that is associated with lower viral load.
abstract: Mechanisms leading to the observed immune dysregulation in chronic HIV infection are not well understood. The MHC-II class ligand, lymphocyte activation gene-3 (LAG-3, CD223), has been implicated in the complex regulation mechanism of immune functions. In this study, we describe a new population of HIV-specific CD8(+) T cells expressing LAG-3. These LAG-3(+)CD8(+) T cells do not display immunophenotypic patterns traditionally attributed to regulatory T cells. The LAG3(+)CD8(+) T cells are CCR7(+),CD127(-), and display heterogeneous surface expressions of CD45RA and CD25. Interestingly, HIV-specific LAG-3(+)CD8(+) T cells do not substantially express CTLA-4 and LAG-3 expression does not correlate with interleukin (IL)-10 or tumor growth factor (TGF)-β production. In addition, HIV-specific LAG3(+)CD8(+) T cells do not produce interferon (IFN-γ) or express CD107a. The frequency of HIV-specific LAG3(+)CD8(+) T cells negative correlated with plasma viral load. Our study introduces a new population of HIV-specific CD8(+) T cells and proposes additional mechanisms of immune regulation in chronic HIV infection.
authors.affiliation: 1 California Department of Public Health, Richmond, California.
authors.forename: José
authors.initials: J
authors.lastname: Peña
authors.forename: Norman G
authors.initials: NG
authors.lastname: Jones
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bousheri
authors.forename: David R
authors.initials: DR
authors.lastname: Bangsberg
authors.forename: Huyen
authors.initials: H
authors.lastname: Cao
mesh_terms: D015703:Antigens, CD / Q000032:analysis*; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D015331:Cohort Studies; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D019562:Viral Load; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; C508609:IL10 protein, human; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma; D000093322:Lymphocyte Activation Gene 3 Protein; C000720326:Lag3 protein, human