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UVB‐irradiated dendritic cells are impaired in their APC function and tolerize primed Th1 cells but not naive CD4+ T cells
Author(s) -
Denfeld Ralf W.,
Hara Hisamichi,
Tesmann Jens P.,
Martin Stefan,
Simon Jan C.
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.69.4.548
Subject(s) - biology , clone (java method) , antigen , t cell , antigen presenting cell , immunology , microbiology and biotechnology , t lymphocyte , cd40 , dendritic cell , interleukin 12 , t cell receptor , cytotoxic t cell , immune system , in vitro , gene , biochemistry
We have shown that low‐dose UVB radiation converts Langerhans cells(LC) from immunogenic to tolerogenic APC. Therefore, we questionedwhether 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, allogeneicT cells; naïve, OVA‐specific TCR‐transgenic T cells fromDO11.10 mice; or primed, antigen‐specific T cells using the Th1 cloneAE7 were analyzed. First, we found low‐dose UVB‐irradiated DC(UVB‐DC) to dose‐dependently (50–200 J/m 2 ) inhibit T‐cellproliferation of naive and primed T cells. In addition, supernatantsharvested from cocultures of UVB‐DC and naive T cells showed markedlyreduced levels of IL‐2 and IFN‐γ and to a lesser degree of IL‐4 andIL‐10, suggesting a preferential down‐regulation of Th1 responses byUVB‐DC. FACS analysis of UVB‐DC revealed no changes in surfaceexpression of MHC, costimulatory, and adhesion molecules. To testtolerance induction, allo‐ or antigen‐specific T cells isolated fromcocultures with unirradiated DC and UVB‐DC were restimulated withunirradiated DC or IL‐2. It is interesting that UVB‐DC inducedantigen‐specific tolerance in the Th1 clone AE7. In contrast, UVB‐DCinduced a partial inhibition of allogeneic T‐cell proliferation but notolerance with similar unresponsiveness to restimulation with IL‐2 andunirradiated DC irrespective of their haplotype. Similar observationswere made when naïve, TCR‐transgenic T cells from DO11.10 micewere used. In conclusion, UVB‐DC are impaired in their APC function andtolerize the primed antigen‐specific Th1 clone AE7 but not naive allo‐or OVA‐specific T cells.