APC-derived cytokines and T cell polarization in autoimmune inflammation
Ilona Gutcher, Burkhard Becher
Ilona Gutcher, Burkhard Becher
Published May 1, 2007
Citation Information: J Clin Invest. 2007;117(5):1119-1127. https://doi.org/10.1172/JCI31720.
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Science in Medicine

APC-derived cytokines and T cell polarization in autoimmune inflammation

Abstract

T cell–mediated autoimmune diseases such as multiple sclerosis and rheumatoid arthritis are driven by autoaggressive Th cells. The pathogenicity of such Th cells has, in the past, been considered to be dictated by their cytokine polarization profile. The polarization of such effector T cells relies critically upon the actions of cytokines secreted by APCs. While Th1 polarization has long been associated with the pathogenesis of autoimmune diseases, recent data obtained in gene-targeted mice and the discovery of Th17 cell involvement in autoimmunity conflict with this hypothesis. In light of these recent developments, we discuss in this review the actions of APC-derived cytokines and their emerging roles in T cell polarization in the context of autoimmune inflammatory responses.

Authors

Ilona Gutcher, Burkhard Becher

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Figure 1

Within the immune synapse formed between APCs and T cells, three signals are required for antigen-specific T cell activation.

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Within the immune synapse formed between APCs and T cells, three signals...
Signal 1 comprises the presentation of antigen peptide, in the context of MHC class II molecules, which is recognized by the antigen-specific TCR. Signal 2 involves the stabilization of the synapse through adhesion molecules and the generation of signals via costimulatory molecules present on the surface of APCs and T cells. CD80/CD86 on APCs interact with their receptor, CD28, on T cells to generate activatory signals, while interaction with cytotoxic T lymphocyte–associated protein 4 (CTLA4) generates inhibitory signals (not shown). Signal 3 is produced by the secretion of cytokines by APCs, which signal via cytokine receptors on T cells in order to polarize them toward an effector phenotype. Ag, antigen.