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

JH Vingerhoets, GL Vanham… - Clinical & …, 1995 - Wiley Online Library
JH Vingerhoets, GL Vanham, LL Kestens, GG Penne, RL Colebunders, MJ Vandenbruaene…
Clinical & Experimental Immunology, 1995Wiley Online Library
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 …
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. CD28CD8+ 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 CD28CD8+ T cells from the patients. In addition, stimulation with plate‐fixed anti‐CD3 induced proliferative responses in highly purified CD28CD8+ 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 CD28CD57+ 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. CD28CD8+ 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.
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