IN-VIVO REACTIVITY OF T-CELL CLONES ISOLATED FROM MICE WITH SYNGENEICGRAFT-VERUS-HOST DISEASE

Syngeneic graft-versus-host disease (SGVHD) has been shown to occur in murine syngeneic radiation bone marrow chimeras following a short cou rse of cyclosporine, To analyze the effector mechanisms present in dis eased 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-K-k in vitro. In addition to I-E(k) re activity, three of the clones exhibited crossreactivity with the super antigen 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 norma lly present in the T cell repertoire of C3H/HeN mice, All SGVHD clones were found to be autoreactive in that they responded to syngeneic sti mulator 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-d ependent, I-E(k)-specific manner in sublethally irradiated, but not no rmal mice, Histological analysis indicated that the clone induced derm al and subcutaneous edema that correlated directly with injection of 1 D5 and not the control clone, Preliminary experiments suggested that t he other three autoreactive clones behaved in a similar manner, These data are consistent with the involvement of a self-class II-specific C D4+ T cell in murine SGVHD.