INHIBITION OF HIV REPLICATION BY CD8-CELLS CORRELATES WITH CD4 COUNTSAND CLINICAL STAGE OF DISEASE( T)

We sought to evaluate the relationship of CD8(+) T cell-mediated inhib ition of autologous HIV replication in vitro to disease stage in HIVindividuals. Depletion of CD8(+) T cells from peripheral blood lymphoc ytes of 16 HIV+ subjects increased the percentage of virus-producing c ultures from 56% to 81%. CD4(+) T cells were purified from 52 HIV+ ind ividuals and cultured alone or in the presence of autologous CD8(+) T cells. In 13 (25%) subjects HIV replication was only detected in the a bsence of CD8(+) T cells (inhibition positive); in 26 (50%) viral repl ication occurred both in the absence and presence of CD8(+) cells (inh ibition negative). In the remaining 13 (25%) subjects, CD8(+) T cell-m ediated 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 ce lls that co-purified with CD4(+) T cells. Detection of inhibitory CD8f T cells was associated with significantly higher CD4 counts and bette r clinical status compared with inhibition-negative subjects. These re sults demonstrate that CD8(+) T cell-mediated inhibition of HIV replic ation correlates with disease stage, and thus may play a role in preve nting disease progression. CD8(+) T cells did not inhibit autologous H IV replication across a semipermeable membrane. Further, the ability o f CD8(+) T cells to prevent HIV replication did not correlate with lys is of autologous CD4(+) T cells. Thus, CD8(+) T cells inhibited autolo gous HIV replication in vitro through a contact mediated non-lytic mec hanism.