Circulating HIV-Specific CD8+ Cytotoxic T Cells Express CD38 and HLA-DR Antigens

CD38, a molecule with multilineage distribution but unknown function, and the MHC class II molecule HLA-DR (DR) have markedly elevated levels of expression on CD8⁺ cells of HIV-infected people. This study investigated the expression of CD38 and DR Ag on circulating HIV-specific CD8⁺ CTL in HIV-seropositive subjects. Purified CD8⁺ lymphocytes from 22 participants in the University of California at Los Angeles Multicenter AIDS Cohort Study were screened for CTL activity against autologous EBV-immortalized lymphoblast targets infected with vaccinia vectors that carried HIV_IIIB gag, pol, and env genes. Sixty-seven percent (14 of 21), 64% (14 of 22), and 9% (2 of 22), respectively, of the subjects had HIV-specific CD8⁺ CTL activity against gag, pol, and env proteins. CD8⁺ cells from 11 of the subjects who had high CTL activity were then FACS-separated using three-color immunofluorescence sorting. Circulating DR^-CD38^- CD8⁺ cells had little activity. Highly purified DR⁺CD38⁺ CD8⁺ cells had higher HIV-specific CTL activity than other CD8⁺ cells. DR⁺CD38^- or DR^-CD38⁺ CD8⁺ cells also mediated significant activity, but only about half as much on a per cell basis as DR⁺CD38⁺ CD8⁺ cells. This is the first report that the CD38 molecule is expressed in vivo on Ag-specific CD8⁺ CTL, and confirms previous reports that DR is expressed on these cells. Both asymptomatic HIV-seropositive subjects (144 ± 132/mm³) and AIDS patients (253 ± 178/mm³) had markedly elevated levels of DR⁺CD38⁺ CD8⁺ cells compared with the levels in HIV-seronegative controls (7 ± 3/mm³). However, the level of anti-HIV CTL activity was not correlated with the level of DR⁺CD38⁺ CD8⁺ cells, indicating that enumeration of this lymphocyte population by flow cytometry most likely will not be a useful surrogate for measuring functional CTL activity. Low levels of HIV-specific CTL activity, especially against gag, were correlated with lower CD4⁺ cell numbers, suggesting that the loss of CD8⁺ T cell cytotoxic activity against HIV that has been reported to occur with advancing HIV disease progression may reflect in part the extent of CD4⁺ cell immunodeficiency in HIV-infected subjects.