TCR-beta transgenic mice fail to mediate a GVHR due to defects of allorecognition and subsequent IL-2 generation.
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.
Rimm
I J
IJ
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Krenger
W
W
Beland
J L
JL
Geller
M C
MC
Di Savino
E
E
Yui
K
K
Katsumata
M
M
Ferrara
J L
JL
D000818:Animals; D006087:Graft vs Host Reaction / Q000235:genetics / Q000276:immunology*; D006183:H-2 Antigens; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000494:pharmacology; D007519:Isoantigens; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology
D006183:H-2 Antigens; D007376:Interleukin-2; D007519:Isoantigens; D016693:Receptors, Antigen, T-Cell, alpha-beta