Immunomodulatory Dendritic Cells Inhibit Th1 Responses and Arthritis Via Different Mechanisms.
From: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Aug 2007
- ISSN: 0022-1767
- Volume: 179
- Issue: 3
- Pages: 1506-15
- Medium: Print
- Language: English
- Citation (JAMA): van Duivenvoorde Leonie M, Han Wanda G H, Bakker Aleida M, et al. Immunomodulatory Dendritic Cells Inhibit Th1 Responses and Arthritis Via Different Mechanisms.. J. Immunol. Aug 2007;179:1506-15
Abstract
Dendritic cells (DCs) are professional APCs which have the unique ability to present both foreign and self-Ags to T cells and steer the outcome of immune responses. Because of these characteristics, DCs are attractive vehicles for the delivery of therapeutic vaccines. Fully matured DCs are relatively well-defined and even used in clinical trials in cancer. DCs also have the potential to influence the outcome of autoimmunity by modulating the underlying autoimmune response. To gain a better appreciation of the abilities and mechanisms by which immunomodulatory DCs influence the outcome of T cell responses, we studied several immunomodulatory DCs (TNF-, IL-10-, or dexamethasone-stimulated bone marrow-derived DCs) side by side for their ability to modulate T cell responses and autoimmune diseases. Our data show that these differentially modulated DCs display a different composition of molecules involved in T cell activation. Although, all DC subsets analyzed were able to inhibit the induction of collagen-induced arthritis, the modulation of the underlying immune response was different. Vaccination with TNF- or IL-10-modulated DCs altered the Th1/Th2 balance as evidenced by the induction of IL-5- and IL-10-secreting T cells and the concomitant reduction of the IgG2a-IgG1 ratio against the immunizing Ag. In contrast, DCs modulated with dexamethasone did not affect the ratio of IL-5-producing vs IFN-gamma-producing T cells and tended to affect the Ab response in a nonspecific manner. These data indicate that distinct mechanisms can be used by distinct DC subsets to change the outcome of autoimmunity.
Mesh Headings (Keywords): Adoptive Transfer, Animals, Arthritis, Experimental, Cells, Cultured, Collagen Type II, Dendritic Cells, Dexamethasone, Immune Tolerance, Male, Mice, Mice, Inbred BALB C, Mice, Inbred DBA, Mice, Transgenic, Th1 Cells
Check for Full Text / PubMed Unique Identifier (PMID): 17641016
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