UVInduced Antigen Specific Immunotolerance

Another of the many consequences of UV irradiation for the immune system is that it also interferes with cell-mediated immunity to allergens by inducing antigen-specific tolerance (Beissert and Granstein 1996, Elmets et al. 1983, Toews et al. 1980, Ullrich 1995a, b). Mice having received an initial immunization through UVB-exposed skin do not mount an immune response after resensitization with the same antigen at a later time (Elments et al. 1983). These same mice showed no compromised immune responses when being sensitized against a different, unrelated antigen, suggesting that UVB irradiation leads to antigen-specific rather than general suppression of the immune system. Subsequent investigations revealed that the induction of antigen-specific tolerogenic suppressor/regulatory T cells was the root of the observed immunosuppression (see "UV-Induced Suppressor/ Regulatory T Cells") and that this also occurred in the model of systemic immuno-suppression.

Once again, there is a correlation between mice and humans in that UVB irradiation can impair CHS responses due to antigen-specific tolerance, depending on the study, in approximately 10% of the human subjects tested (Yoshikawa et al. 1990). In accordance with the mouse models, tolerance induced in these few volunteers was antigen specific, since they reacted with pronounced CHS responses on subsequent sensitization with a nonrelated antigen. Even higher percentages of human volunteers developing tolerance when the antigen was initially applied onto skin areas exposed to erythemogenic UVB doses were reported in a further study (Cooper et al. 1992). These variations maybe due to the different UV irradiation protocols used.Neverthe-less, both studies demonstrate the existence of a subtype of humans who develop tolerance when the sensitizing antigen is first applied onto UVB-exposed skin.

Erythemogenic UVB doses not only cause the emigration and subsequent depletion of Langerhans' cells in the skin but also result in the infiltration of CD1a- HLA-DR+ CD36+ macrophages in the skin (Cooper et al. 1992). These macrophages can then activate autoreactive T cells (Cooper et al. 1985, 1986), specifically, CD4+ "sup-pressor-inducer" cells, which in turn induce the maturation of suppressor T cells (Baadsgaard et al. 1988, 1990). In addition, these macrophages, which also express CD11b+, can release the immunosuppressive cytokine IL-10 at considerable concentrations, probably representing the major source for epidermal IL-10 protein in human UV-exposed skin (Kang et al. 1994). This is of particular relevance in light of the fact that IL-10 seems to be play a major role in UVB-induced immunosuppression (see "UV-Induced Systemic Immunosuppression"). In vitro studies have shown that on UVB exposure, the macrophages infiltrating the epidermis can also induce CD4+ T lymphocytes, which lack expression of the IL-2 receptor alpha chain (Stevens et al. 1995). Down-regulation of the IL-2 receptor alpha chain seems to be connected with effects caused by transforming growth factor, another immunosuppressive mediator.

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