Amelioration of acute graft-versus-host disease and re-establishment of tolerance by short-term treatment with an anti-TCR antibody.

摘要: We investigated whether tolerance can be re-established in mice with graft-vs-host disease (GVHD) by using a short-term, T cell-depleting treatment an anti-TCR-alpha beta mAb. GVHD was induced 950-rad-irradiated AKR (H-2k, Mls-1a) injecting 5 x 10(6) cell-depleted bone marrow cells together either 10(7) or 2 lymph node (LN) from BALB/c (H-2d, and Mls-1b). that received LN exhibited severe form of acute GVHD, which all died day 60. In this mAb completely ameliorated the induction when initiated on 0 (a total 800 micrograms/mouse administered days 0,5, 10). When same protocol begun 10, it had no therapeutic effect. However, delayed very effective reversing less injection donor cells. Recipient given prophylactic achieved host-specific association clonal deletion host Mls-1a-reactive V 6+ contrast, spleen recipient recovered mild as result contained considerable proportion cells, despite healthy appearance these mice. A MLR assay revealed responded well to Mls-1a Ag but not H-2k Ag, contrast apparent responses untreated controls both Ags. addition, beta-treated specific reduction cytotoxicity against blasts. Collectively, data indicate short-term having mAb, starting even after onset, re-establish tolerance, at least host-histo-compatibility Ag.