Inhibition of HIV replication by CD8 + T cells correlates with CD4 counts and clinical stage of disease

SUMMARY We sought to evaluate the relationship of CD8 + T cell‐mediated inhibition of autologous HIV replication in vitro to disease stage in HIV + individuals. Depletion of CD8 + T cells from peripheral blood lymphocytes of 16 HIV + subjects increased the percentage of virus‐producing cultures from 56% to 81%. CD4 + T cells were purified from 52 HIV + individuals and cultured alone or in the presence of autologous CD8 + T cells. In 13 (25%) subjects HIV replication was only detected in the absence of CD8 + T cells (inhibition positive); in 26 (50%) viral replication occurred both in the absence and presence of CD8 + cells (inhibition negative). In the remaining 13 (25%) subjects, CD8 + T cell‐mediated inhibitory activity could not be evaluated because stimulation of their purified CD4 + T cells did not result in p24 production. In some virus culture‐negative individuals, the inability to demonstrate HIV replication was due to the presence of low numbers of CD8 + T cells that co‐purified with CD4 + T cells. Detection of inhibitory CD8 + T cells was associated with significantly higher CD4 counts and better clinical status compared with inhibition‐negative subjects. These results demonstrate that CD8 + T cell‐mediated inhibition of HIV replication correlates with disease stage, and thus may play a role in preventing disease progression. CD8 + T cells did not inhibit autologous HIV replication across a semipermeable membrane. Further, the ability of CD8 + T cells to prevent HIV replication did not correlate with lysis of autologous CD4 + T cells. Thus, CD8 + T cells inhibited autologous HIV replication in vitro through a contact mediated non‐lytic mechanism.