CYTOTOXIC T-LYMPHOCYTES THAT KILL AUTOLOGOUS CD4(-1 INFECTION() LYMPHOCYTES ARE ASSOCIATED WITH CD4(+) LYMPHOCYTE DEPLETION IN HIV)

Human immunodeficiency virus type 1 (HIV-1)-infected individuals, but not HIV-seronegative controls, have non-HLA-restricted T-cell receptor alpha beta(+) CD8(+) cytotoxic T-lymphocytes (CTL) that kill activate d uninfected CD4(+) lymphocytes. In vitro stimulation of peripheral bl ood mononuclear cells from HIV-1-infected individuals with concanavali n A (Con A) or by coculture with phytohemagglutinin-activated autologo us lymphoblasts induced CTL that killed autologous and heterologous CD 4(+) lymphocytes, but not Con A-activated CD8(+) lymphocytes or Epstei n-Barr virus (EBV)-transformed B lymphocytes. EBV did not stimulate su ch CTL in two subjects tested, although stimulation with Con A or auto logous lymphoblasts induced CTL activity against CD4(+) lymphocytes in both subjects. CTL activity against autologous CD4(+) lymphocytes var ied over time; killing of heterologous CD4(+) lymphocytes was often hi gher than that of autologous CD4(+) lymphocytes. HIV-infected individu als with Con A-inducible CTL against autologous CD4(+) lymphocytes los t more CD4(+) lymphocytes within 6 months of testing than HIV-infected individuals with no such CTL (p <.01). The mean (+/-SD) decrease in C D4(+) lymphocyte counts in a group of HIV-infected individuals with CT L activity against autologous CD4(+) lymphocytes was 121 +/- 84, or 36 %, of total CD4(+) lymphocytes over 6 months. In contrast, there was n o significant change in mean CD4(+) lymphocyte count over 6 months in a group of HIV-infected individuals without CTL activity against autol ogous CD4(+) lymphocytes. In some HIV-infected individuals, CTL activi ty against autologous CD4(+) lymphocytes fell coincident with a drop i n CD4(+) lymphocyte number in vivo. The same individuals maintained CT L activity against CD4(+) lymphocytes from an uninfected individual, c onsistent with elimination of autologous CD4(+) targets of CTL from th e HIV-infected individuals in vivo. These results suggest that CTL aga inst CD4(+) lymphocytes contribute to CD4(+) lymphocyte loss in HIV in fection.