Open AccessIncreased cytolytic T lymphocyte activity and decreased B7 responsiveness are associated with CD28 down‐regulation on CD8 + T cells from HIV‐infected subjects
Author(s) -
VINGERHOETS J. H.,
VANHAM G. L.,
KESTENS L. L.,
PENNE G. G.,
COLEBUNDERS R. L.,
VANDENBRUAENE M. J.,
GOEMAN J.,
GIGASE P. L.,
BOER M.,
CEUPPENS J. L.
Publication year - 1995
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1995.tb03717.x
Subject(s) - cd28 , cytotoxic t cell , cd8 , interleukin 21 , biology , immunology , t lymphocyte , t cell , cd3 , microbiology and biotechnology , antigen , immune system , in vitro , biochemistry
SUMMARY 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‐2Rα. 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‐2Rα nod 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.