Increased cytolytic T lymphocyte activity and decreased B7 responsiveness are associated with CD28 down-regulation on CD8+ T cells from HIV-infected subjects

Clin Exp Immunol. 1995 Jun;100(3):425-33. doi: 10.1111/j.1365-2249.1995.tb03717.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / analysis
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • B7-1 Antigen / immunology*
  • CD28 Antigens / immunology*
  • CD57 Antigens
  • CD8-Positive T-Lymphocytes / immunology*
  • Cytotoxicity, Immunologic*
  • Down-Regulation
  • Female
  • Flow Cytometry
  • HIV Infections / immunology*
  • Humans
  • Immunity, Cellular
  • Immunophenotyping
  • Ligands
  • Male
  • Middle Aged
  • Receptors, Interleukin-2 / metabolism
  • Receptors, Transferrin / metabolism
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • B7-1 Antigen
  • CD28 Antigens
  • CD57 Antigens
  • Ligands
  • Receptors, Interleukin-2
  • Receptors, Transferrin