       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).

