T cell apoptosis in human immunodeficiency virus type 2- and simian immunodeficiency virus-infected macaques.
Recent evidence suggests that T cell apoptosis could be involved in the pathogenesis of HIV infection. In addition, lymphocyte apoptosis has been described in SIV-infected macaques that developed simian AIDS. To investigate further the role of apoptosis in AIDS pathogenesis, we studied lymphocytes of HIV-2-infected cynomolgus macaques that did not develop simian AIDS. We compared apoptosis of lymphocytes from animals infected with non-pathogenic HIV-2 to that in macaques infected with pathogenic SIV. Unfractionated peripheral blood mononuclear cells of SIV- and HIV-2-infected macaques showed evidence of apoptosis by electron microscopy, flow cytometry (terminal dUTP nick end labelling) and visualization of DNA fragmentation. Between 30-50% apoptotic cells could be detected in SIV-infected animals, compared to approximately 30% in HIV-2-infected and 5-12% in uninfected monkeys. However, separation of PBMC into T cell subpopulations revealed striking differences in apoptosis between SIV- and HIV-2-infected macaques. In SIV-infected monkeys both CD4 and CD8 cells underwent apoptosis to a large extent. In contrast, in the HIV-2-infected macaques apoptosis was restricted to the CD8 cell compartment. The lack of apoptosis in CD4 cells of healthy HIV-2-infected macaques implies an important role for CD4 cell apoptosis in AIDS pathogenesis.
Department for Virology and Immunology, German Primate Center, Göttingen.
U
U
Dittmer
H
H
Petry
C
C
Stahl-Hennig
T
T
Nisslein
M
M
Spring
W
W
Luke
W
W
Bodemer
F J
FJ
Kaup
G
G
Hunsmann
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology*; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D005434:Flow Cytometry; D015658:HIV Infections / Q000503:physiopathology*; D015498:HIV-2 / Q000472:pathogenicity*; D006801:Humans; D008252:Macaca fascicularis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000503:physiopathology*; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity*