Graft-versus-host mortality induced by noncytolytic CD4 super(+) T cell clones specific for non-H-2 antigens

The relative contribution of individual non-H-2 Ag and of T cell subsets that initiate graft-vs-host reaction (GVHR) as well as the mechanism responsible for histopathologic lesions are still a matter of debate. To address these questions and to favor the selection of T cells primed in vivo against non-H-2 Ag important in GVHR we derived T cell clones from spleens of (DBA/2 x B10.D2)F1 (H-2 super(d)) mice developing this reaction after the graft of B10.D2 (H-2 super(d)) cells incompatible for numerous non-H-2 Ag plus Mls super(a). The pattern of reactivity of eight selected clones against cells from different strains of mice including (BXD)RI strains indicated that one CD4 super(+) clone is specific for Mls super(a) and seven additional clones (six CD4 super(+) and one CD8 super(+)) are specific for four different non-H-2 Ag (Ag.I-IV) and proliferate in an H-2-restricted manner. The reaction against a single non H-2 Ag is sufficient to provoke lethal GVHR.