The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/1/123/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 1, January 5, 1998 123-128

Brief Definitive Reports

Maximal Proliferation of Cytotoxic T Lymphocytes Requires Reverse Signaling through Fas Ligand

Ivy Suzuki and Pamela J. Fink

From the Department of Immunology, University of Washington, Seattle, Washington 98195

Fas ligand (FasL/CD95L) is best known for its role in delivering apoptotic signals through its receptor, Fas (APO-1/CD95). In this study, we present evidence that FasL has a second role as a signaling receptor. Alloantigen-specific proliferation by multiple FasL– murine CTL lines is depressed compared to that of FasL+ CTL lines. FasL– CTLs kill efficiently on a per recovered cell basis and can achieve wild-type levels of proliferation upon stimulation by optimal doses of anti-CD3, suggesting the lack of a costimulatory signal during antigen stimulation. To test this hypothesis directly, soluble FasIgG, a fusion protein of murine Fas and human IgG1, was added to FasL+ CTLs to demonstrate that blocking cell surface Fas–FasL interactions mimics the depression observed for FasL– CTLs. In addition, plate-bound FasIgG in conjunction with suboptimal anti-CD3 stimulation augments proliferative signals in FasL+ but not FasL– CTLs. In contrast to these results with CD8+ T cells, alloantigen-stimulated FasL– CD4+ T cells proliferate vigorously compared to FasL+ cells. These data demonstrate that reverse signaling through FasL is required for CTLs to achieve maximal proliferation and may provide clues to differences in the homeostatic regulation of activated CD4+ and CD8+ T cells during an immune response.

Address correspondence to Dr. Pamela J. Fink, University of Washington, Department of Immunology, Box 357650, Rm H574A, Seattle, WA 98195. Phone: 206-685-3608; Fax: 206-616-7237; E-mail: pfink{at}u.washington.edu


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