In vivo reactivity of T cell clones isolated from mice with syngeneic graft-versus-host disease.

Syngeneic graft-versus-host disease (SGVHD) has been shown to occur in murine syngeneic radiation bone marrow chimeras following a short course of cyclosporine. To analyze the effector mechanisms present in diseased animals, four T cell clones (1D5, 1D8, 1C10, 2D8) were isolated from the spleens of C3H/HeN mice late in the disease course by cloning on irradiated syngeneic spleen cells. These clones were CD4+, alpha beta TCR+ and responded to I-Kk in vitro. In addition to I-Ek reactivity, three of the clones exhibited crossreactivity with the superantigen MIs 1a (mtv 7). Clones 1D5 and 1C10 were found to express TCR V beta chains (V beta 4 and V beta 8.1, respectively), which are normally present in the T cell repertoire of C3H/HeN mice. All SGVHD clones were found to be autoreactive in that they responded to syngeneic stimulator cells in the absence of xenogeneic serum proteins. To test in vivo activity, the 1D5 SGVHD clone was injected into the hind footpad of mice where it was shown to induce footpad swelling in a cell dose-dependent, I-Ek-specific manner in sublethally irradiated, but not normal mice. Histological analysis indicated that the clone induced dermal and subcutaneous edema that correlated directly with injection of 1D5 and not the control clone. Preliminary experiments suggested that the other three autoreactive clones behaved in a similar manner. These data are consistent with the involvement of a self-class II-specific CD4+ T cell in murine SGVHD.