LACK OF CHRONIC IMMUNE ACTIVATION IN HIV-INFECTED CHIMPANZEES CORRELATES WITH THE RESISTANCE OF T-CELLS TO FAS APO-1 (CD95)-INDUCED APOPTOSIS AND PRESERVATION OF A T-HELPER-1 PHENOTYPE/

Chimpanzees are one of the few species, along with humans, susceptible to persistent HIV-1 infection. However, HIV-infected chimpanzees do n ot exhibit the marked immune system alterations seen in humans and rem ain relatively resistant to AIDS. In humans, HIV infection leads to un responsiveness of T cells in response to TCR stimulation, associated w ith increased T cell death by apoptosis. In an effort to understand so me of the mechanisms used to limit lentivirus infection in African non human primates, we compared apoptosis in infected humans vs chimpanzee s in CD4 and CD8 T cells in relation with the expression of Bcl-2 and Fas molecules. The intensity of apoptosis in CD4 and CD8 T cells from infected chimpanzees was very low, was not inducible by several TCR-de pendent activators, and was comparable to that detected in noninfected chimpanzees. Moreover, CD45RO(+) and HLA-DR(+) subsets, which were sh own to exhibit ex vivo a high propensity to undergo apoptosis in infec ted humans, were not modified in infected chimpanzees. Interestingly, in contrast to the situation found in infected humans, Fas ligation by agonistic Abs or recombinant human Fas ligand on CD4 and CD8 T cells from infected chimpanzees did not induce apoptosis in these subsets ev en when Bcl-2 was down-regulated. Finally, this resistance to apoptosi s was associated with the predominance of CD3 T cells with a Th1 pheno type. Together these observations argue for a strong relationship amon g the absence of chronic immune stimulation in HIV-1-infected chimpanz ees, the normal control of lymphocyte survival, and the resistance to disease progression.