Suppression of allograft responses by combining alloantigen-specific i.v. pre-sensitization with suboptimal doses of XXXX .

@entity2047 @entity19 @entity3446 @entity5041 @entity1140
C57BL/6 (B6) @entity19 were injected i.v. with class I H-2-disparate B10.QBR spleen cells (10(7)/ @entity19 ). This regimen, termed donor alloantigen-specific i.v. pre-sensitization (DSP), induced almost complete reduction of the anti-B10.QBR mixed lymphocyte reaction (MLR) that has been regarded to represent a cytotoxic T lymphocyte (CTL)-independent graft rejection pathway. Because the DSP regimen failed to affect the generation of CTL responses, it did not prolong graft survival. Repeated (four or 11 times) administration in vivo (during 5 or 18 days) of @entity3446 at suboptimal doses (0.5-2.0 mg/kg/day) failed to eliminate the capacities to exhibit MLR as well as to generate CTL responses. The suppression of CTL responses was achieved only through the combination of these two treatments. It was also shown that prolongation of skin graft survival was not induced by either of a single DSP or @entity3446 treatment alone, but by the combination of these. Potent suppression of CTL responses was also induced when a single DSP was combined with repeated injection of a suboptimal dose (0.75 mg/kg/day) of another immunosuppressive drug, @entity1140 , instead of @entity3446 . However, there was a substantial difference in cellular mechanisms underlying the suppression of CTL responses by the above two different combinations. Under conditions in which lymphoid cells from @entity19 receiving the treatments with DSP plus @entity1140 failed to generate CTL responses, the addition of recombinant @entity2047 ( @entity5041 ) to cultures restored the CTL generation, suggesting that CTL precursors themselves are not attenuated by the combined treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
