The Fas receptor in HIV infection: expression on peripheral blood lymphocytes and role in the depletion of T cells.
OBJECTIVE
To analyse the role of the apoptosis-inducing Fas receptor in the depletion of CD4+ and CD8+ T cells in HIV-infected individuals.


METHODS
Peripheral blood lymphocytes (PBL) obtained from HIV-infected subjects of all 1993 Centers for Disease Control and Prevention (CDC) stages and from non-infected controls were examined. A two-colour cytofluorometry was employed using monoclonal antibodies against Fas receptor (CD95) in combination with the surface markers CD4, CD8, CD28, CD26 and CD45RO. CD4+ and CD8+ T-cell-enriched PBL were used as target cells to assess their susceptibility to lysis by CD4+ cytotoxic T lymphocytes (CTL) which kill via the Fas pathway.


RESULTS
Fas+PBL are more elevated in HIV-infected individuals than in HIV-negative controls and increase significantly from CDC stages A to C. Whereas Fas+CD4+ and Fas-CD4+ T-cell populations decline in parallel with the progression of HIV infection, the Fas+CD8+, but not of the Fas-CD8+ fraction, significantly increases. The Fas+CD8+ lymphocytes are susceptible to Fas-mediated lysis as they are efficiently killed by Fas-ligand+CD4+CTL.


CONCLUSIONS
The Fas receptor may contribute, but not as a unique cause, to the decline of CD4+ T cells in HIV-infected individuals. This and the significant increase of the number of Fas+ CD8+ T cells indicates that Fas-mediated immune regulation is disturbed.
Gehri
R
R
Institute for Medical Microbiology, University of Basel, Switzerland.
Hahn
S
S
Rothen
M
M
Steuerwald
M
M
Nuesch
R
R
Erb
P
P
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D008211:Lymphocyte Cooperation; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019014:fas Receptor / Q000096:biosynthesis*
D015703:Antigens, CD; D019014:fas Receptor