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The fact that the TCR repertoire selected in the thymus can be altered in the periphery helps explain the presence of rogue autoreactive T cells [24]. Surface expression of the costimulatory molecule CD40, thought to be restricted to APCs, has been observed recently on neural cells, endothelial cells, adipocytes, and subsets of CD4 and CD8 T cells. Activation of CD40 expressed by the mature CD4 Th subset, designated Th40 cells, induces RAG‐1/RAG‐2‐mediated rearrangement of both TCR α‐ and β‐chains in the periphery. This refutes early dogma of the immutability of the TCR repertoire and its antigen specificity after T cells emigrate from the thymus. The fact that Th40 cells can undergo multiple cycles of TCR revision multiplies the risk of developing autoreactive TCRs, including ones recognizing unique self‐neoantigens. The finding that adoptively transferred Th40 cells induced antigen‐specific type 1 diabetes mellitus (T1DM) in non‐obese diabetic severe combined immunodeficiency mice confirms their immunogenic function. Thus, TCR revision to recognize autoantigens represents a new paradigm, explaining autoreactive peripheral T cells.