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* Department of Immunology and Center for Cancer Immunology Research, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030; and
Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston, TX 77225
UV exposure suppresses the immune response to a variety of microbial, fungal, and viral Ags. In addition, UV radiation is a complete carcinogen and the immune suppression induced by UV radiation is a major risk factor for skin cancer induction. In this study, we examined the mechanisms underlying the induction of immune suppression and tolerance induction by UV radiation. Transferring lymph nodes cells from UV-irradiated, FITC-sensitized mice into normal recipients transferred immune tolerance. Contrary to expectations, the cell responsible was an FITC+, IL-10-secreting, CD19+, B220+ B cell. Because the lipid mediator of inflammation, platelet-activating factor (PAF) is released by UV-irradiated keratinocytes and is essential for the induction of immune suppression, we determined its role in tolerance induction. When UV-irradiated mice were injected with PCA 4248, a selective PAF receptor (PAFR) antagonist, transfer of tolerance was suppressed. However, immune suppression was not transferred when FITC+ cells from the draining lymph nodes of UV-irradiated, PAFR-deficient donor mice were injected into the recipients. Because PCA 4248 also blocks serotonin receptor binding, we measured the effect that blocking both serotonin and PAFR binding has on the transfer of immune suppression. Only when both PAF and serotonin binding were blocked could we inhibit tolerance induction. These data identify a novel function for PAF and serotonin in modulating immune function, the activation of immunoregulatory B cells.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the National Cancer Institute (CA75575, CA88943, and CA112660). S.N.B. was supported by a C. J. Martin Fellowship (No. 307726) from the National Health and Medical Research Council of Australia. The animal and flow cytometry facilities at the M. D. Anderson Cancer Center were supported in part by a core grant from the National Cancer Institute (CA16672).
2 Y.M. and S.N.B. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Stephen E. Ullrich, Department of Immunology-902, University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. E-mail address: sullrich{at}mdanderson.org
4 Abbreviations used in this paper: CHS, contact hypersensitivity; PAF, platelet-activating factor; PAFR, PAF receptor; WT, wild type; MFI, mean fluorescence intensity.
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