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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4885-4891.
Prepublished online as a Blood First Edition Paper on March 3, 2005; DOI 10.1182/blood-2004-12-4980.
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TRANSPLANTATION
Emergent autoimmunity in graft-versus-host disease
Elizabeth Tivol,
Richard Komorowski, and
William R. Drobyski
From the Bone Marrow Transplant Program and the Departments of Medicine and Pathology, Medical College of Wisconsin, Milwaukee, WI.
Donor T-cell recognition of host alloantigens presented by host antigen-presenting cells (APCs) is necessary for the induction of graft-versus-host disease (GVHD), but whether direct alloreactivity is sufficient for the propagation of GVHD is unknown. In this study, we demonstrate that GVHD cannot be effectively propagated through the direct pathway of allorecognition. Rather, donor T-cell recognition of antigens through the indirect pathway is necessary for the perpetuation of GVHD. Furthermore, GVHD results in the breaking of self tolerance, resulting in the emergence of donor T cells that can cause autoimmune disease in syngeneic recipients. Notably, GVHD-induced autoreactivity is donor APC dependent, transferable into secondary hosts, and involves cells of the innate immune system. These results indicate that donor T-cell--mediated pathologic damage during GVHD becomes donor APC dependent and provide a mechanistic explanation for the long-standing observation that GVHD is associated with autoimmune clinical manifestations. (Blood. 2005;105:4885-4891)
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