Amelioration of acute GVHD disease and reestablishment of tolerance by short term treatment with anti TCR antibody

T. Maeka, M. Eto, T. Lin, Y. Nishimura, YY Kong, K. Nomoto, J. Immunol

Research output: Contribution to journalArticle

Abstract

We investigated whether tolerance can be reestablished in mice with graft‐versus‐host disease (GVHD) by using a short‐term, T‐celldepleting treatment with an anti‐TCR‐αβ mAb. GVHD was induced in 950‐rad—irradiated AKR mice (H‐2k, Mls‐1a) by injecting 5 × 106 T celldepleted bone marrow cells together with either 107 or 2 × 106 lymph node (LN) cells from BALB/c mice (H‐2d, 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 × 105 donor LN cells. Recipient mice given prophylactic antiTCR‐αβ treatment achieved host‐specific tolerance in association with clonal deletion of host Mls‐1a‐reactive Vβ+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 Vβ6+T cells, despite the healthy appearance of these mice. A MLR assay showed that the spleen cells from these mice responded well to Mls‐1a Ag but not to H‐2k 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 indicated 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. (Copyright 1994. The Journal of Immunology.)

Original languageEnglish
Pages (from-to)257-258
Number of pages2
JournalLiver Transplantation and Surgery
Volume1
Issue number4
DOIs
Publication statusPublished - Jul 1995
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Surgery
  • Hepatology

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