Human immunodeficiency virus type 1-and cytomegalovirus-specific cytotoxicT lymphocytes can persist at high frequency for prolonged periods in the absence of circulating peripheral CD4(+) T cells

CD4(+) T cells are thought to be critical in the maintenance of virus-speci fic CD8(+) cytotoxic T-cell (CTL) responses. In human immunodeficiency viru s type 1 (HIV-1) infection, a selective decline in HIV-1-specific CTL as th e CD4+ T-cell count decreases has been reported. Using HLA-peptide tetramer ic complexes, we show the presence at high frequency of HIV-1- and cytomega lovirus-specific CD8+ T cells when the peripheral CD4(+) T-cell count was l ow or zero in three HIV-l-infected patients. No direct virus-specific CD8()-mediated effector activity was seen in these subjects, suggesting antigen unresponsiveness, although tetramer-sorted cells could be expanded in vitr o in the presence of interleukin-2 into responsive effector cells. Thus, vi rus specific CD8(+) T cells can be maintained in the peripheral circulation at high frequency in the absence of circulating peripheral CD4(+) T cells, but these cells may lack direct effector activity. Strategies designed to overcome this antigen unresponsiveness may be of value in therapies for the treatment of AIDS.