Increased CD95/Fas-induced apoptosis of HIV-specific CD8(+) T cells.
Why HIV-specific CD8(+) T cells ultimately fail to clear or control HIV infection is not known. We show here that HIV-specific CD8(+) T cells exhibit increased sensitivity to CD95/Fas-induced apoptosis. This apoptosis is 3-fold higher compared to CMV-specific CD8(+) T cells from the same patients. HIV-specific CD8(+) T cells express the CD45RA(-)CD62L(-) but lack the CD45RA(+)CD62L(-) T cell effector memory (T(EM)) phenotype. This skewing is not found in CMV- and EBV-specific CD8(+) T cells in HIV-infected individuals. CD95/Fas-induced apoptosis is much higher in the CD45RA(-)CD62L(-) T(EM) cells. However, cytotoxicity and IFNgamma production by HIV-specific CD8(+) T cells is not impaired. Our data suggest that the survival and differentiation of HIV-specific CD8(+) T cells may be compromised by CD95/Fas apoptosis induced by FasL-expressing HIV-infected cells.
Mueller
Y M
YM
Department of Microbiology and Immunology, MCP Hahnemann University, Philadelphia, Pennsylvania 19129, USA.
De Rosa
S C
SC
Hutton
J A
JA
Witek
J
J
Roederer
M
M
Altman
J D
JD
Katsikis
P D
PD
D000328:Adult; D017209:Apoptosis; D002454:Cell Differentiation; D018920:Coculture Techniques; D003587:Cytomegalovirus / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000032:analysis; D019041:L-Selectin / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000032:analysis; D008264:Macrophages / Q000821:virology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology*; D019562:Viral Load; D019014:fas Receptor / Q000502:physiology*
D019014:fas Receptor; D019041:L-Selectin; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens