TCR-beta transgenic mice fail to mediate a GVHR due to defects of allorecognition and subsequent IL-2 generation
Rimm, I.J.; Krenger, W.; Beland, J.L.; Geller, M.C.; Di Savino, E.; Yui, K.; Katsumata, M.; Ferrara, J.L.
Bone Marrow Transplantation 17(5): 835-842
1996
ISSN/ISBN: 0268-3369 PMID: 8733706 Document Number: 461406
All T cells of TCR-beta transgenic mice bear a single TCR-beta 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-beta 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-beta mice. All tested strains of TCR-beta mice failed to mediate a substantial GVHR across multiple H-2 barriers. In addition, mixtures of cells from several strains of TCR-beta mice only generated mild GVHRs. Sensitive tests of in vitro allorecognition show that lymphoid cells from TCR-beta 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-beta mice fail to use exogenous IL-2 appropriately in their response to alloantigen. We conclude that the fixed TCR-beta 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.