RELATION OF IMPAIRED LYMPHOCYTE PROLIFERATIVE FUNCTION TO OTHER MAJORHUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-INDUCED IMMUNOLOGICAL CHANGES

Human immunodeficiency virus (HIV) type 1 (HIV-1) induces impairment o f immune function reflected in reduced lymphocyte proliferative respon ses. Many other immune changes are induced by HIV-1, but their relatio nship to lymphocyte functional defects is not known. The present study was designed to correlate functional defects with other HIV disease p arameters. Cryopreserved samples from 118 HIV-1-positive subjects and 40 seronegative individuals were examined. The main findings were that impaired proliferative responses to mitogens correlated with (i) decr eased cell surface expression of the interleukin-2 receptor (CD25), (i i) increased expression of HLA-DR antigens on CD4 cells, (iii) reduced CD4 and increased CD8 cell numbers, and (iv) increased levels of seru m immune complex dissociated p24 antigen. However, impaired function w as not associated with increased serum neopterin, beta 2-microglobulin , or soluble interleukin-2 receptor or with CD38 antigen expression on lymphocytes. In summary, proliferative functional impairment correlat ed with some, but not all, immunological changes associated with HIV-1 infection. Most of the phenotypic markers that correlated with altere d function are cell surface molecules with significant roles in lympho cyte proliferation and were associated primarily with CD4 cells, compa tible with the view that dysregulation of CD4 cells is responsible for impaired function.