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

Takeshi Maeda, Masatoshi Eto, Tesu Lin, Yousuke Nishimura, Young Yun Kong, Kenichi Nomoto, Kikuo Nomoto

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 with an anti-TCR-αβ mAb. GVHD was induced in 950-rad-irradiated AKR mice (H-2(k), Mls-1a) by injecting 5 x 106 T cell-depleted bone marrow cells together with either 107 or 2 x 106 lymph node (LN) cells from BALB/c mice (H-2(d), and Mls-1b). AKR mice that received 107 LN cells exhibited a severe form of acute GVHD, in which all mice died by day 60. In this severe form of GVHD, treatment with anti-TCR-αβ mAb completely ameliorated the induction of GVHD when initiated on day 0 (a total of 800 μg/mouse administered on days 0, 5, and 10). When the same protocol was begun on day 10, it had no therapeutic effect. However, this delayed treatment with anti- TCR-αβ mAb was very effective in reversing a less severe form of GVHD that was induced by the injection of 2 x 106 donor LN cells. Recipient mice given prophylactic anti-TCR-αβ treatment achieved host-specific tolerance in association with clonal deletion of host Mls-1a-reactive Vβ6+ T cells. In contrast, spleen cells from recipient mice that recovered from the mild form of GVHD as a result of the delayed anti-TCR-αβ treatment contained a considerable proportion of the Vβ6+ T cells, despite the healthy appearance of these mice. A MLR assay revealed that the spleen cells from these mice responded well to Mls-1a Ag but not to H-2(k) Ag, in contrast with the apparent responses of spleen cells from untreated GVHD controls to both Ags. In addition, cells from the anti-TCR-αβ-treated mice exhibited a specific reduction in cytotoxicity against AKR blasts. Collectively, these data indicate that a short-term treatment of mice having GVHD with an anti-TCR- αβ mAb, starting even after disease onset, can re-establish host-specific tolerance, at least to the host-histocompatibility Ag.

Original languageEnglish
Pages (from-to)4311-4320
Number of pages10
JournalJournal of Immunology
Volume153
Issue number9
Publication statusPublished - Nov 1 1994

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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