Early Aged T-Cells in Immune-Mediated Diseases

摘要

Early loss of thymic function may be crucial for the development of immune-mediated diseases. According to nthis concept premature collapse of thymic output is compensated by homeostatic proliferation of peripheral T-cells, driven nby recognition of self antigens and finally resulting in the expansion of autoreactive, senescent T-cell clones. Such nsenescent T-cells are characterized by the loss of the co-stimulatory receptor CD28 and the gain of new nimmunomodulatory molecules such as natural killer cell receptors and toll-like receptors. The immune system may ncompensate for these changes by regulatory mechanisms, including the evolvement of regulatory T-cells. However, the naging process may also affect these regulatory T-cells leading to a second “hit” of the immune system. Current therapeutic napproaches in patients with immune-mediated diseases target common end pathways of inflammation, driven by nproinflammatory cytokines and effector cells. Future directions will include the aim to reset the immune system, by nrestoring the ability to repopulate the immune system with young and adaptable lymphocytes as well as by strengthening nthe effect of regulatory T-cells.