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Sclerodermatous chronic graft‐versus‐host disease induced by host T‐cell‐mediated autoimmunity
Author(s) -
Lee You Jeong,
Min Hye Sook,
Kang Eun Ha,
Park Hyo Jin,
Jeon Yoon Kyung,
Kim Ju Hyun,
Wu Hong Gyun,
Lee EunBong,
Park ChungGyu,
Yoon SungSoo,
Park Seong Hoe,
Jung Kyeong Cheon
Publication year - 2012
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2011.46
Subject(s) - graft versus host disease , autoimmunity , immunology , chimera (genetics) , t cell , biology , inflammation , autoimmune disease , immune system , stem cell , microbiology and biotechnology , antibody , biochemistry , gene
Despite a long‐standing hypothesis that chronic graft‐versus‐host disease (cGVHD) is an autoimmune disorder, most mouse models of cGVHD have been developed on the assumption that donor T cells are essential for its development. Here we show that cGVHD may be caused by autoreactive host T cells in mice that have been lethally irradiated and grafted with T‐cell‐depleted allogeneic bone marrow cells. In this chimera, host T cells derived from radioresistant intrathymic T‐cell precursors caused dermal fibrosis and periportal inflammation, without the requirement for donor T cells. The lack of host DCs within the thymus after high‐dose irradiation allowed autoreactive host T cells to escape thymic negative selection. Moreover, the homeostatic expansion of these T cells may augment their autoreactivity. These findings indicate that host T‐cell‐mediated cGVHD is an autoimmune process that occurs following the grafting of T‐cell‐depleted BM cells into hosts with functioning thymuses. We propose, based on the present data, that host T‐cell‐dependent autoimmunity is a potential mechanism by which cGVHD is induced.