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
Gougeon, M.L.; Lecoeur, H.; Boudet, F.; Ledru, E.; Marzabal, S.; Boullier, S.; Roué, R.; Nagata, S.; Heeney, J.
Journal of Immunology 158(6): 2964-2976
1997
ISSN/ISBN: 0022-1767 PMID: 9058836 Document Number: 474964
This study compared apoptosis in infected humans vs chimpanzees in CD4+ and CD8+ T cells in relation to 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-dependent activators, and was comparable to that detected in noninfected chimpanzees. Moreover, CD45RO+ and HLA-DR+ subsets, which were shown to exhibit ex vivo a high propensity to undergo apoptosis in infected 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 even when Bcl-2 was down-regulated. Finally, this resistance to apoptosis was associated with the predominance of CD3+ T cells with the Th1 phenotype. Together these observations argue for a strong relationship among the absence of chronic immune stimulation in HIV-1 infected chimpanzees, the normal control of lymphocyte survival, and the resistance to disease progression.