Induction of CD95 ligand expression on T lymphocytes and B lymphocytes and its contribution to apoptosis of CD95-up-regulated CD4+ T lymphocytes in macaques by infection with a pathogenic simian/human immunodeficiency virus.
Using an established SIV/HIV-C2/1-infected cynomolgus monkey model displaying stable CD4+ T cell depletion, the kinetics of apoptosis and the levels of expression of CD95 membrane-associated CD95L on lymphocytes were investigated to test the involvement of the CD95/CD95L system in CD4+ T lymphocyte loss in vivo. Rapid depletion of CD4+ T cells occurred up to 2 weeks after infection, with chronic CD4+ T lymphopenia thereafter. During the initial CD4+ T cell loss, which was accompanied by viraemia, about 90% of the peripheral CD4+ T cell subset underwent spontaneous apoptotic cell death during 24 h of culture. Increased expression of CD95 was observed on both CD4+ and CD8+ T cell subsets, with CD95 expression on CD8+ cells declining rapidly, but high CD95 expression being maintained on CD4+ cells. Since CD95L was expressed on CD8+ T cells, B cells and to a lesser extent on CD4+ T cells, this suggests that CD95-mediated apoptosis might be controlled in an autocrine/paracrine fashion.
Sasaki
Y
Y
Department of Safety Research on Biologics, National Institute of Infectious Diseases, Tokyo, Japan. yuko@nih.go.jp
Ami
Y
Y
Nakasone
T
T
Shinohara
K
K
Takahashi
E
E
Ando
S
S
Someya
K
K
Suzaki
Y
Y
Honda
M
M
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D053222:Fas Ligand Protein; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology; D008231:Lymphopenia / Q000276:immunology; D008252:Macaca fascicularis; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology*; D019562:Viral Load; D019014:fas Receptor / Q000096:biosynthesis*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor