HIV-related alterations in CD8 cell subsets defined by in vitro survival characteristics

Previously we showed that over 50% of CD8 cells from HIV-infected persons do not survive in 3-day cultures of mononuclear cells; this loss occurred preferentially in subsets with phenotypes indicative of in vivo activation. In the studies reported here, we asked if cytokines enhanced CD8 cell survival. Of IL1, IL2, IL4, IL6, tumor necrosis factor, and interferon-gamma only IL2 specifically enhanced CD8 survival in the HIV group, compared to the control group. Further studies thus focused on characterizing CD8 cell survival in the presence of IL2. In both study groups, three subsets of CD8 cells were identified based on in vitro survival: (a) those surviving in culture medium alone (survivors), (b) those surviving only when IL2 was included in the culture medium (IL2-dependent survivors), and (c) those failing to survive even in the presence of IL2 (nonsurvivors). By dual-color cytofluorometry, the CD8 survivor subset was similar in the two study groups, and expressed nonactivated phenotypes (Leu8+, CD45RA+, HLA-DR-). The IL2-dependent survivor subset was also similar in the two study groups and expressed the phenotypes Leu8-, CD45RA+, CD57+, HLA-DR+, and CD38+, suggesting prior activation. The CD8 nonsurvivor subset, in contrast, was markedly different in the study groups: compared to the control group, the HIV group contained significantly higher proportions of CD8 cells expressing the phenotypes Leu8-, CD57+, and HLA-DR+, also suggesting activation. These findings indicate that, in HIV infection, the activated CD8 cell subsets that do not survive in medium alone consist of a "normal" component that requires IL2 for survival and an "abnormal" component that does not survive even in IL2.