Significance
The adaptive immune system has the potential to generate a self-reactive response, which can eventually lead to an autoimmune disease. To avoid this outcome, T lymphocytes with high-affinity, self-reactive antigen receptors are blocked from entering the mature T-cell pool (negative selection). Given this mechanism for removing dangerous high-affinity T cells, we wondered whether autoimmunity is more likely to be caused by chronic stimulation of low-affinity T cells or by stimulation of a few high-affinity T cells that escaped negative selection. In this paper, we show that T cells with an affinity just above the selection threshold can bypass negative selection and have the highest potential to cause an experimental autoimmune disease.
Lacking colonic mucosal innervation correlated with increased inflammatory immune cell status, microbial dysbiosis, and higher incidence of postoperative enterocolitis in HSCR patients. Mucosal nerve fibers might serve as a prognostic marker for enterocolitis development and offer new therapeutic intervention strategies.
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