EXPRESSION OF COSTIMULATORY MOLECULE CD28 ON T-CELLS IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION - FUNCTIONAL AND CLINICAL CORRELATIONS

To study the functional integrity of T cells from human immunodeficiency virus type 1 (HIV-1)-infected persons, CD4(+) and CD8(+) cells were examined for proliferation and secretion of interleukin-2 (IL-2) in response to staphylococcal superantigens and antibodies to CD3 and the alpha beta T cell receptor. A functional defect within CD8(+) but not within CD4(+) cells from HIV-1-infected persons was observed. Within CD8(+) cells, proliferation and secretion of IL-2 was restricted to cells expressing the costimulatory molecule CD28. Such cells were proportionally reduced in HIV-1-infected persons. In patients with advanced immunodeficiency, however, evidence of functional derangement was found also within the CD28(+) CD8(+) cells. In a cross-sectional study of 73 HIV-infected persons and 15 controls, a significant correlation was observed between the number of CD28(+) CD8(+) cells and the presence of HIV-related disease. Our results suggest that regulation of expression of CD28 may play an important role in the immunopathogenesis of AIDS.