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 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-subset-specific 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 SIVsmmPBj14-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.
Bostik
P
P
Department of Pathology and Laboratory Medicine, Winship Cancer Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA. pbostik@emory.edu
Brice
G T
GT
Greenberg
K P
KP
Mayne
A E
AE
Villinger
F
F
Lewis
M G
MG
Ansari
A A
AA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D016664:Cercocebus; D018450:Disease Progression; D006801:Humans; D019394:Ki-67 Antigen / Q000097:blood; D008213:Lymphocyte Activation; D008251:Macaca; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000201:enzymology / Q000276:immunology* / Q000503:physiopathology*; D015302:Simian Immunodeficiency Virus; D019098:Telomerase / Q000097:blood*
D019394:Ki-67 Antigen; D019098:Telomerase