Inverse correlation of telomerase activity/proliferation of CD4(+) T lymphocytes and disease progression in simian immunodeficiency virus-infected nonhuman primates

Both increased lymphocyte renewal with subsequent exhaustion of the immune system and impaired T-cell renewal have been put forth to account for CD4() T-cell depletion and development of AIDS in HIV-1-infected humans and SIV -infected nonhuman primates. In the present study, telomeric terminal restr iction fragment length and telomerase activity were used as measures of pro liferative activity of T lymphocytes from three nonhuman primate species be fore and after being infected with SIV. In peripheral blood T cells, our da ta show both species and T-cell-subset specific differences in proliferativ e activity accompanied by different patterns of disease progression. A sign ificant postinfection increase in telomerase/proliferative activity in CD4( +) T cells from seropositive sooty mangabeys and from normal progressor rhe sus macaques was associated with asymptomatic infection or delayed disease progression, respectively, whereas a decrease in telomerase/proliferative a ctivity detected in CD4(+) T cells postinfection from SIVsmmPBj14-infected pigtailed macaques was associated with rapid CD4(+) T-cell depletion acid d isease progression. The levels of telomerase activity observed in CD4+ T ce lls from peripheral blood closely parallelled those seen in CD4+ T cells in lymph node samples from selected animals. Our data suggest that an increas e in proliferative activity of T lymphocytes in vivo may be associated with a favorable course of SIV infection in nonhuman primates.