Role of Regulatory T Cells in the Treatment of Multiple Sclerosis, pp. 57-78
Authors: (K. Szklany, T.C. Koehler, W. van Eden, Utrecht University, The Netherlands)
Abstract: In the last years knowledge of regulatory T cells has expanded. They play a role in autoimmune disease but it is still unclear how they suppress auto-reactive T cells exactly. The possibilities to use regulatory T cells in the treatment of MS are discussed in this chapter. The focus will be on the function of HLA-G and CD4+CD25+ T cells expressing FoxP3 and CTLA-4. Two types of Tregs with different ways of suppression are known. Adaptive Tregs are induced in the periphery and mainly secrete TGF-β and IL-10. These cytokines mediate suppression of T cells through induction of FoxP3. Natural Tregs are generated in the thymus and suppress T cells through HLA-G, CTLA-4 and FoxP3. HLA-G interrupts the signalling in APCs and T cells resulting in suppression. FoxP3 blocks the expression of IL-2 and consequently inhibits proliferation of T cells. The expression of FoxP3 is induced by TGF-β. TGF-β also induces CD4+CD25- T cells to convert into CD4+CD25+ T cells which express FoxP3 and hence suppress T cell proliferation. The suppression mechanism of CTLA-4 is still unknown. It might be a positive feedback with TGF-β resulting in increased expression of FoxP3 or a block of co-stimulatory molecules on APCs causing reduced secretion of cytokines following reduced activation of T cells.