UVB-irradiated dendritic cells induce nonproliferating, regulatory type T cells.
It is well established that low-dose UVB radiation inhibits the antigen-presenting cell (APC) function of murine Langerhans cells in vivo and converts them from immunogenic to tolerogenic APC. Recently, we have shown that UVB-irradiated murine bone marrow-derived dendritic cells (UVB-DC) suppressed proliferation of naive and primed T cells, but tolerized primed T cells only. To examine the underlying mechanism for these differences, naive OVA(323-339)-peptide-specific, TCR-transgenic T cells from DO11.10 mice were analyzed following coculture with unirradiated DC or UVB-DC. First, we found that UVB-DC inhibit OVA-specific T cell proliferation UVB dose and antigen dose dependently. Analysis of T cells cocultured with both, unirradiated and UVB-DC, revealed an activated T cell phenotype with increased expression of CD25 and CD69 by FACS. Supernatants harvested from cocultures with UVB-DC showed reduced levels of IFN-gamma, IL-2 and IL-4, but not TGF-beta, compared with unirradiated DC as determined by ELISA. Furthermore, these T cells did not proliferate upon restimulation. Interestingly, addition of these nonproliferating T cells to cocultures of naive T cells and freshly prepared unirradiated DC inhibited T cell proliferation depending on the number of added nonproliferating T cells. Also, in supernatants, increased levels of TGF-beta were found. Therefore, our data indicate that UVB-DC propagate T cells with a regulatory function. Since regulatory T cells are characterized by enhanced TGF-beta secretion and increased CTLA-4 expression, we currently investigate the role of CTLA-4 phenotypically and functionally. In conclusion, we have shown that UVB-DC inhibit proliferation of naive OVA-specific T cells. These T cells, exhibiting an activated phenotype and increased TGF-beta production, suppress proliferation of naive T cells cocultured with unirradiated DC. These results suggest that UVB-DC induce nonproliferating, regulatory type T cells.
Simon
J C
JC
Department of Dermatology, University of Freiburg, Freiburg, Germany. jancsimon@haut.ukl.uni-freiburg.de
Hara
H
H
Denfeld
R W
RW
Martin
S
S
D000818:Animals; D002455:Cell Division / Q000502:physiology / Q000528:radiation effects; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D006801:Humans; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects