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

I. J. Rimm, W. Krenger, J. L. Beland, M. C. Geller, E. Di Savino, K. Yui, M. Katsumata, J. L.M. Ferrara

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)835-842
Number of pages8
JournalBone Marrow Transplantation
Volume17
Issue number5
StatePublished - May 1996
Externally publishedYes

Keywords

  • Bone marrow transplantation
  • Graft-versus-host disease
  • Transgenic mice

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