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Original Article

^a Department of Dermatology, University of Mainz, D-55101 Mainz, Germany
^b Institute of Immunology, University of Mainz, D-55101 Mainz, Germany
^c Department of Dermatology, University of Erlangen-Nürnberg, D-91052 Erlangen, Germany
Dept. of Dermatology, University of Mainz, D-55101 Mainz, Germany.49-6131-1747354149-6131-173541

The functional properties of dendritic cells (DCs) are strictly dependent on their maturational state. To analyze the influence of the maturational state of DCs on priming and differentiation of T cells, immature CD83^– and mature CD83⁺ human DCs were used for stimulation of naive, allogeneic CD4⁺ T cells. Repetitive stimulation with mature DCs resulted in a strong expansion of alloreactive T cells and the exclusive development of T helper type 1 (Th1) cells. In contrast, after repetitive stimulation with immature DCs the alloreactive T cells showed an irreversibly inhibited proliferation that could not be restored by restimulation with mature DCs or peripheral blood mononuclear cells, or by the addition of interleukin (IL)-2. Only stimulation of T cells with mature DCs resulted in an upregulation of CD154, CD69, and CD70, whereas T cells activated with immature DCs showed an early upregulation of the negative regulator cytotoxic T lymphocyte–associated molecule 4 (CTLA-4). These T cells lost their ability to produce interferon , IL-2, or IL-4 after several stimulations with immature DCs and differentiated into nonproliferating, IL-10–producing T cells. Furthermore, in coculture experiments these T cells inhibited the antigen-driven proliferation of Th1 cells in a contact- and dose-dependent, but antigen-nonspecific manner. These data show that immature and mature DCs induce different types of T cell responses: inflammatory Th1 cells are induced by mature DCs, and IL-10–producing T cell regulatory 1–like cells by immature DCs.

Key Words: dendritic cells • regulatory T cells • T helper type 1 cells • interleukin 10 • T cell differentiation

^{Abbreviations used in this paper:CTLA, CTL-associated molecule; DC, dendritic cell; iDC, immature DC; mDC, mature DC; ICOS, inducible costimulator; Tr, regulatory T.}

© 2000 The Rockefeller University Press

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