HIV-specific CD8+ T cells exhibit markedly reduced levels of Bcl-2 and Bcl-xL.
Human immunodeficiency virus-specific CD8(+) T cells are highly sensitive to spontaneous and CD95/Fas-induced apoptosis, and this sensitivity may impair their ability to control HIV infection. To elucidate the mechanism behind this sensitivity, in this study we examined the levels of antiapoptotic molecules Bcl-2 and Bcl-x(L) in HIV-specific CD8(+) T cells from HIV-infected individuals. Bcl-2 expression was markedly decreased in HIV-specific CD8(+) T cells compared with CMV-specific and total CD8(+) T cells from HIV-infected individuals as well as total CD8(+) T cells from healthy donors. CD8(+) T cell Bcl-2 levels inversely correlated with spontaneous and CD95/Fas-induced apoptosis of CD8(+) T cells from HIV-infected individuals. HIV-specific CD8(+) T cells also had significantly lower levels of Bcl-x(L) compared with CMV-specific CD8(+) T cells. Finally, IL-15 induces both Bcl-2 and Bcl-x(L) expression in HIV-specific and total CD8(+) T cells, and this correlated with apoptosis inhibition and increased survival in both short- and long-term cultures. Our data indicate that reduced Bcl-2 and Bcl-x(L) may play an important role in the increased sensitivity to apoptosis of HIV-specific CD8(+) T cells and suggest a possible mechanism by which IL-15 increases their survival.
Petrovas
Constantinos
C
Departments of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
Mueller
Yvonne M
YM
Dimitriou
Ioannis D
ID
Bojczuk
Paul M
PM
Mounzer
Karam C
KC
Witek
James
J
Altman
John D
JD
Katsikis
Peter D
PD
D000276:Adjuvants, Immunologic / Q000502:physiology; D017209:Apoptosis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002470:Cell Survival / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology / Q000821:virology; D006801:Humans; D019409:Interleukin-15 / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000097:blood*; D015854:Up-Regulation / Q000276:immunology; D051020:bcl-X Protein; D019014:fas Receptor / Q000276:immunology
D000276:Adjuvants, Immunologic; C494811:BCL2L1 protein, human; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D019409:Interleukin-15; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D019014:fas Receptor