TCR-β transgenic mice fail to mediate a GVHR due to defects of allorecognition and subsequent IL-2 generation

All T cells of TCR-β transgenic mice bear a single TCR-β chain and consequently the diversity of the TCR may be reduced by as much as one million-fold. Despite this limited diversity, many measures of lymphocyte function in these mice are normal. We have previously demonstrated that lymphoid cells from TCR-β mice are unable to mediate an intense graft-versus-host response (GVHR). In order to investigate the mechanism of this hyporesponsiveness, we studied in vivo allorecognition in diverse strains of TCR-β mice. All tested strains of TCR-β mice failed to mediate a substantial GVHR across multiple H-2 barriers. In addition, mixtures of cells from several strains of TCR-β mice only generated mild GVHRs. Sensitive tests of in vitro allorecognition show that lymphoid cells from TCR-β mice respond less vigorously to alloantigen as measured both by decreased proliferation and decreased IL-2 production in a MLR. In addition, cells from TCR-β mice fail to use exogenous IL-2 appropriately in their response to alloantigen. We conclude that the fixed TCR-β chain causes a defective response to alloantigen, which is measured as decreased IL-2 generation and utilization, and that this abnormality results in a decreased GVHR.