Document 0540 DOCN M9590540 TI Increased cytolytic T lymphocyte activity and decreased B7 responsiveness are associated with CD28 down-regulation on CD8+ T cells from HIV-infected subjects. DT 9509 AU Vingerhoets JH; Vanham GL; Kestens LL; Penne GG; Colebunders RL; Vandenbruaene MJ; Goeman J; Gigase PL; De Boer M; Ceuppens JL; Department of Infection and Immunity, Institute of Tropical; Medicine, Antwerp, Belgium. SO Clin Exp Immunol. 1995 Jun;100(3):425-33. Unique Identifier : AIDSLINE MED/95292389 AB The CD28 receptor on CD4+ and CD8+ T cells interacts with B7 molecules on antigen-presenting cells (APC) to generate essential costimulatory signals. The cytolytic potential of CD8+ T cells could be linked to CD28 expression. Since HIV induces dysfunction of both CD4+ and CD8+ T cells, we evaluated CD28 expression and function in both subsets during HIV infection. CD28 expression on CD8+ T cells from HIV+ subjects was strongly reduced in a disease stage-related fashion. CD28- CD8+ T cells preferentially expressed CD57 and CD11b, but lacked CD26 and IL-2R alpha. The CD8+ T cells from the patients showed a significantly reduced proliferative response to co-stimulation with cell-bound anti-CD3 and B7. Nevertheless, when stimulated with plate-fixed anti-CD3, CD8+ T cells from HIV-infected subjects proliferated normally, and normal levels of IL-2R alpha and transferrin-receptor could be induced on CD28- CD8+ T cells from the patients. In addition, stimulation with plate-fixed anti-CD3 induced proliferative responses in highly purified CD28- CD8+ T cells from both HIV- and HIV+ persons. Furthermore, the increased cytotoxic activity of peripheral blood mononuclear cells (PBMC) from HIV+ subjects, measured in an anti-CD3 redirected assay, was predominantly exerted by CD28- CD57+ T cells. CD4+ T cells from the patients showed a slight but significant CD28 down-regulation and were slightly hyporesponsive to B7 co-stimulation. Decrease of CD28 on CD8+ T cells from HIV+ subjects is associated with an impaired response to co-stimulation via B7. CD28- CD8+ T cells from seropositives, however, are not completely inert, since they contain in vivo activated CTL and they can be additionally activated through a B7-independent stimulation. DE Adult Aged Antigens, CD/ANALYSIS Antigens, CD28/*IMMUNOLOGY Antigens, Differentiation, T-Lymphocyte/ANALYSIS B-Cell Activation Antigen/*IMMUNOLOGY *Cytotoxicity, Immunologic CD8-Positive T-Lymphocytes/*IMMUNOLOGY Down-Regulation (Physiology) Female Flow Cytometry Human HIV Infections/*IMMUNOLOGY Immunity, Cellular Immunophenotyping Ligands Male Middle Age Receptors, Interleukin-2/METABOLISM Receptors, Transferrin/METABOLISM Support, Non-U.S. Gov't T-Lymphocyte Subsets/*IMMUNOLOGY T-Lymphocytes, Cytotoxic/*IMMUNOLOGY JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).