The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/4/1285/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 8, April 19, 1999 1285-1294

Articles

A Critical Role for Fas Ligand in the Active Suppression of Systemic Immune Responses by Ultraviolet Radiation

Laurie L. Hill, Vijay K. Shreedhar, Margaret L. Kripke, and Laurie B. Owen-Schaub

From the Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030

Induction of antigen-specific suppression elicited by environmental insults, such as ultraviolet (UV)-B radiation in sunlight, can inhibit an effective immune response in vivo and may contribute to the outgrowth of UV-induced skin cancer. Although UV-induced DNA damage is known to be an initiating event in the immune suppression of most antigen responses, the underlying mechanism(s) of such suppression remain undefined. In this report, we document that Fas ligand (FasL) is critical for UV-induced systemic immune suppression. Normal mice acutely exposed to UV exhibit a profound suppression of both contact hypersensitivity and delayed type hypersensitivity (DTH) reactions and the development of transferable antigen-specific suppressor cells. FasL-deficient mice exposed to UV lack both transferable suppressor cell activity and primary suppression to all antigens tested, with the exception of the DTH response to allogeneic spleen cells. Interestingly, suppression of this response is also known to occur independently of UV-induced DNA damage. Delivery of alloantigen as protein, rather than intact cells, restored the requirement for FasL in UV-induced immune suppression of this response. These results substantiate that FasL/Fas interactions are essential for systemic UV-induced suppression of immune responses that involve host antigen presentation and suggest an interrelationship between UV-induced DNA damage and FasL in this phenomenon. Collectively, our results suggest a model whereby UV-induced DNA damage disarms the immune system in a manner similar to that observed in immunologically privileged sites.

Key Words: Fas ligand • ultraviolet radiation • immunosuppression • CD95 • T suppressor cells

Address correspondence to Laurie B. Owen-Schaub, Department of Immunology, Box 178, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. Phone: 713-792-8735; Fax: 713-745-1633; E-mail: lowensch{at}mdanderson.org

V.K. Shreedhar's current address is the Department of Medicine, Harvard Medical School, 300 Longwood Ave., Elders 1220, Boston, MA 02115.

Abbreviations used: CHS, contact hypersensitivity; DTH, delayed type hypersensitivity; FasL, Fas ligand; NR, nonirradiated; RT, reverse transcriptase; UVR, UV-irradiated.


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