INCREASED CYTOLYTIC T-LYMPHOCYTE ACTIVITY AND DECREASED B7 RESPONSIVENESS ARE ASSOCIATED WITH CD28 DOWN-REGULATION ON CD8(-CELLS FROM HIV-INFECTED SUBJECTS() T)

The CD28 receptor on CD4(+) and CD8(+) T cells interacts with B7 molec ules on antigen-presenting cells (APC) to generate essential costimula tory signals. The cytolytic potential of CD8(+) T cells could be linke d to CD28 expression, Since HIV induces dysfunction of both CD4(+) and CD8(+) T cells, we evaluated CD28 expression and function in both sub sets during HIV infection. CD28 expression on CD8(+) T cells from HIV subjects was strongly reduced in a disease stage-related fashion, CD2 8(-)CD8(+) T cells preferentially expressed CD57 and CD11b, but lacked CD26 and IL-2R alpha. The CD8(+) T cells from the patients showed a s ignificantly reduced proliferative response to co-stimulation with cel l-bound anti-CD3 and B7. Nevertheless, when stimulated with plate-fixe d anti-CD3, CD8(+) T cells from HIV-infected subjects proliferated nor mally, and normal levels of IL-2R alpha and transferrin-receptor could be induced on CD28(-)CD8(+) T cells from the patients. In addition, s timulation with plate-fixed anti-CD3 induced proliferative responses i n highly purified CD28(-)CD8(+) T cells from both HIV- and HIV+ person s. Furthermore, the increased cytotoxic activity of peripheral blood m ononuclear cells (PBMC) from HIV+ subjects, measured in an anti-CD3 re directed assay, was predominantly exerted by CD28(-)CD57(+) T cells. C D4(+) T cells from the patients showed a slight but significant CD28 d own-regulation and were slightly hyporesponsive to B7 co-stimulation. Decrease of CD28 on CD8(+) T cells from HIV+ subjects is associated wi th an impaired response to co-stimulation via B7. CD28(-)CD8(+) T cell s from seropositives, however, are not completely inert, since they co ntain in vivo activated CTL and they can be additionally activated thr ough a B7-independent stimulation.