The death receptor Fas (CD95/APO-1) mediates the deletion of T lymphocytes undergoing homeostatic proliferation.
Murine T cells adoptively transferred into syngeneic lymphopenic recipients undergo proliferation. Despite continued cell division, this lymphopenia-induced or homeostatic proliferation of a limited number of transferred T cells does not fill the T cell compartment. The continued expansion of the transferred T cells, even after stable T cell numbers have been reached, suggests that active cell death prevents further increase in T cell number. In this study, we show that wild-type T cells undergoing homeostatic proliferation are sensitive to Fas-mediated cell death. In the absence of Fas, T cells accumulate to significantly higher levels after transfer into lymphopenic recipients. Fas is, thus, a principal regulator of the expansion of peripheral T cells in response to self-peptide/MHC during T cell homeostasis. As Fas-deficient lpr mice manifest no significant abnormalities in thymic negative selection or in foreign Ag-induced peripheral T cell deletion, their lymphadenopathy may result from unrestrained homeostatic proliferation.
Fortner
Karen A
KA
Immunobiology Division, Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405, USA.
Budd
Ralph C
RC
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D017637:Clonal Deletion / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000502:physiology*
D018398:Homeodomain Proteins; D019014:fas Receptor; C064658:RAG-1 protein