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Ultraviolet Irradiation Suppresses T Cell Activation via Blocking TCR-Mediated ERK and NF-B Signaling Pathways

Tumorimmunology Program, German Cancer Research Center, Heidelberg, Germany

UV irradiation is carcinogenic and immunosuppressive. Previous studies indicate that UV-mediated alteration of APCs and induction of suppressor T cells play a critical role in UV-induced immune suppression. In this study, we show that UV irradiation can directly (independently of APCs and suppressor T cells) inhibit T cell activation by blocking TCR-mediated phosphorylation of ERK and IB via overactivation of the p38 and JNK pathways. These events lead to the down-modulation of c-Jun, c-Fos, Egr-1, and NF-B transcription factors and thereby inhibit production of cytokines, e.g., IL-2, IL-4, IFN-, and TNF-, upon TCR stimulation. We also show that UV irradiation can suppress preactivated T cells, indicating that UV irradiation does not only impair T cell function in response to T cell activation, but can also have systemic effects that influence ongoing immune responses. Thus, our data provide an additional mechanism by which UV irradiation directly suppresses immune responses.

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