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(Journal of Leukocyte Biology. 2001;69:548-554.)
© 2001 by Society for Leukocyte Biology

UVB-irradiated dendritic cells are impaired in their APC function and tolerize primed Th1 cells but not naive CD4+ T cells

Ralf W. Denfeld^*, Hisamichi Hara^*,, Jens P. Tesmann^*, Stefan Martin^* and Jan C. Simon^*

^* Department of Dermatology, Albert-Ludwigs-Universität, Freiburg, Germany; and
Department of Dermatology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan

Correspondence: Dr. R. W. Denfeld, Department of Dermatology, Albert-Ludwigs-Universität, Hauptstrasse 7, 79104 Freiburg, Germany. E-mail: denfeld{at}haut.ukl.uni-freiburg.de

We have shown that low-dose UVB radiation converts Langerhans cells (LC) from immunogenic to tolerogenic APC. Therefore, we questioned whether low-dose UVB irradiation of bone marrow-derived dendritic cells (DC) alters their APC function, thereby inducing tolerance in T cells. To address this issue, cocultures of DC; and naïve, allogeneic T cells; naïve, OVA-specific TCR-transgenic T cells from DO11.10 mice; or primed, antigen-specific T cells using the Th1 clone AE7 were analyzed. First, we found low-dose UVB-irradiated DC (UVB-DC) to dose-dependently (50–200 J/m²) inhibit T-cell proliferation of naive and primed T cells. In addition, supernatants harvested from cocultures of UVB-DC and naive T cells showed markedly reduced levels of IL-2 and IFN- and to a lesser degree of IL-4 and IL-10, suggesting a preferential down-regulation of Th1 responses by UVB-DC. FACS analysis of UVB-DC revealed no changes in surface expression of MHC, costimulatory, and adhesion molecules. To test tolerance induction, allo- or antigen-specific T cells isolated from cocultures with unirradiated DC and UVB-DC were restimulated with unirradiated DC or IL-2. It is interesting that UVB-DC induced antigen-specific tolerance in the Th1 clone AE7. In contrast, UVB-DC induced a partial inhibition of allogeneic T-cell proliferation but no tolerance with similar unresponsiveness to restimulation with IL-2 and unirradiated DC irrespective of their haplotype. Similar observations were made when naïve, TCR-transgenic T cells from DO11.10 mice were used. In conclusion, UVB-DC are impaired in their APC function and tolerize the primed antigen-specific Th1 clone AE7 but not naive allo- or OVA-specific T cells.

Key Words: T lymphocyte • anergy • tolerance • costimulatory molecules

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