title: Functional dichotomy of CD4+ T helper lymphocytes in asymptomatic human immunodeficiency virus infection.
abstract: The majority of asymptomatic, human immune deficiency virus seropositive (HIV+) individuals exhibit a defect in CD4+ T helper cell (Th) function that is selective for responses to recall antigens, but not to HLA alloantigens. The CD4-dependent Th response to HLA alloantigens (Allo) can be mediated by two distinct Th pathways: self-restricted CD4+ Th that recognize allogeneic determinants processed and presented by autologous or self accessory or antigen-presenting cells (sAC); and allo-restricted, CD4+ Th that recognize allogeneic determinants directly on allogeneic accessory or antigen-presenting cells (aAC). In contrast, the Th response to recall antigens requires CD4+ Th and sAC and is therefore limited to the major histocompatibility complex (MHC) self-restricted pathway. Peripheral blood leukocytes from 56 asymptomatic HIV+ patients that exhibited a selective defect in CD4+ Th function were analyzed to determine whether the Th response to Allo was entirely functional, or whether one of the CD4-mediated components of the Allo Th response was also defective. By depletion of AC and/or CD8+ Th subsets (to analyze CD4+ Th function), we demonstrated that HIV+ patients who were selectively deficient in Th function to recall antigens were also unresponsive to Allo presented by autologous AC (HLA self-restricted Th pathway), but retained Allo Th activity presented by allogeneic AC (allo-restricted CD4+ Th pathway). These findings indicate that the CD4+ Th defect seen in the majority of asymptomatic, HIV+ individuals is not limited to recall antigens, but also extends to the component of the response to HLA alloantigens that involves the self-restricted, CD4+ Th pathway. Thus, the Th defect observed in asymptomatic, HIV+ patients does not involve a CD4+ Th defect per se, but is limited to the HLA self-restricted component of Th function.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: M
authors.initials: M
authors.lastname: Clerici
authors.forename: C S
authors.initials: CS
authors.lastname: Via
authors.forename: D R
authors.initials: DR
authors.lastname: Lucey
authors.forename: E
authors.initials: E
authors.lastname: Roilides
authors.forename: P A
authors.initials: PA
authors.lastname: Pizzo
authors.forename: G M
authors.initials: GM
authors.lastname: Shearer
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D016176:T-Lymphocyte Subsets / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D006680:HLA Antigens; D007376:Interleukin-2