A Non - H - 2 Locus Determines the Inabi l i ty to Induce Letha l Graft - Versus - Host Disease

One of the possible consequences of the graft-versus-host reaction (GVHR) 1 in animals and man is runt disease or acute graft-versus-host (GVH) disease (GVHD). It is frequently fatal and produces a variety of symptoms, which include atrophy of the skin and the gastrointestinal mucosa and hypoplasia of the hemopoietic and lymphoid tissues manifested by anemia and immunodeficiency, respectively (1, 2). Donor T cells are known to be responsible for the induction of runt disease (3, 4). However, the mechanisms by which T cells induce the pathological symptoms of runt disease are poorly understood. Another possible outcome of the GVHR is a chronic GVHD which can lead to different conditions, such as lymphadenopathy (5, 6), immune complex glomerulonephritis (6, 7), and formation of multiple autoantibodies (8-11). Previous analyses performed in nonirradiated Fa mice have shown that there are two minimal, essential requirements for the induction of the symptoms of chronic GVttD: immunocompetent T lymphocytes must be present in the donor cell inoculum and they must be able to react to incompatible H-2 structures of the recipient (5-7, 9, 11). Undefined genetic factors of the T cell-donor strain decide which of the two kinds of GVHD develop in the Fa hybrid recipients (5-7, 11). This point is best exemplified by previous studies on groups of identical (C57BL/6 × DBA/2)F1 or (C57BL/10 × DBA/2)F1 hybrid mice as recipients o f T cells from the donor strains DBA/2, C57BL/ 6, C57BL//10, and B10.D2. When DBA/2 T cells were injected into these Fi hybrids, a syndrome ensued that resembled systemic lupus erythematosus (7, 11). However, lymphadenopathy only rarely, and runt disease never, belonged to the spectrum of abnormalities induced by the donor DBA/2 (5, 11).