Exploring the signalling pathways promoting T cell effector responses in chronic inflammation

Abstract  Over the last decade, it has become clear that T helper cell differentiation is determined by a programme of gene transcription, which is in turn dictated by signalling pathways emanating from both T cell antigen receptors and cytokine receptors. This model has provided an experimental framework for exploring the molecular mechanisms through which T cell effector responses initiate autoimmunity, chronic inflammatory disease, and allergy. Much less clear are the processes that regulate T helper cell differentiation and effector responses in established chronic inflammatory diseases such as rheumatoid arthritis. This review describes recent experimental data which suggest that the inflammatory process profoundly influences T cell receptor and cytokine signal transduction pathways in such a way as to attenuate both immunoregulatory and host defence mechanisms on the one hand, while promoting cell survival and effector responses on the other. These findings are consistent with a model in which the inflammatory response is initiated primarily by antigen-driven T cell effector responses, while the chronic phase of the disease process is sustained by cytokine-driven effector responses.