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. 2020 Mar 9;130(4):1625–1628. doi: 10.1172/JCI136139

Figure 1. Model of impaired tolerance in GVHD pathogenesis.

Figure 1

Acute GVHD simultaneously damages nonhematopoietic cells enforcing central and peripheral tolerance in the thymus and lymph nodes. In the thymus, mTECs ectopically express a broad range of tissue-restricted antigens under the control of the autoimmune regulator AIRE. mTECs promote the negative selection of autoreactive T cells and development of central tolerance. In the periphery, lymph node FRCs also show promiscuous expression of tissue-restricted antigens and facilitate the suppression of mature autoreactive T cells, thereby maintaining peripheral tolerance. Acute GVHD targets both mTECs in the thymus and FRCs in lymph nodes, thereby creating a dangerous situation in which large numbers of autoreactive T cells are left to sustain tissue damage during chronic GVHD. TRA, tissue-restricted antigen; GVHD, graft-versus-host disease; mTECs, medullary thymic epithelial cells; AIRE, autoimmune regulator; FRCs, fibroblastic reticular cells.