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Inverse Correlation of Telomerase Activity/Proliferation of CD4+ T Lymphocytes and Disease Progression in Simian Immunodeficiency Virus-Infected Nonhuman Primates

Bostik Pavel; Brice, Gary T.; Greenberg, Kenneth P.; Mayne, Ann E.; Villinger, Francois; Lewis, Mark G.; Ansari, Aftab A.
JAIDS Journal of Acquired Immune Deficiency Syndromes: June 1st, 2000
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Summary: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 restriction fragment length and telomerase activity were used as measures of proliferative activity of T lymphocytes from three nonhuman primate species before and after being infected with SIV. In peripheral blood T cells, our data show both species and T-cell-subsetspecific differences in proliferative activity accompanied by different patterns of disease progression. A significant postinfection increase in telomerase/proliferative activity in CD4+ T cells from seropositive sooty mangabeys and from normal progressor rhesus macaques was associated with asymptomatic infection or delayed disease progression, respectively, whereas a decrease in telomerase/proliferative activity detected in CD4+ T cells postinfection from SIVsmmPBj 14-infected pigtailed macaques was associated with rapid CD4+ T-cell depletion and disease progression. The levels of telomerase activity observed in CD4+ T cells from peripheral blood closely parallelled those seen in CD4+ T cells in lymph node samples from selected animals. Our data suggest that an increase in proliferative activity of T lymphocytes in vivo may be associated with a favorable course of SIV infection in nonhuman primates.

Address correspondence and reprint requests to Pavel Bostik, Department of Pathology and Laboratory Medicine, Winship Cancer Center, Emory University School of Medicine, 1365B Clifton Road, Atlanta, GA 30322;

The information in this paper does not necessarily reflect the position or the policy of the U. S. government and no official endorsement should be inferred.

Manuscript received October 27, 1999; accepted April 21, 2000.

© 2000 Lippincott Williams & Wilkins, Inc.