Lethal graft-vs-host disease induced by a class II MHC antigen only disparity is not mediated by cytotoxic T cells

Dwain L Thiele, S. E. Bryde, P. E. Lipsky

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Treatment of C57BL/6J (B6) murine splenocytes with L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) selectively removes NK cells, CTL precursors, and the capacity to cause lethal graft-vs-host disease (GVHD) in irradiated B6 x DBA/2 F1 mice. In contrast, alloantigen-induced L3T4(+) Th cell function has been shown to be relatively preserved after exposure to this agent. The present studies assessed the effects of Leu-Leu-OMe treatment of donor cells on induction of lethal GVHD in other murine strain combinations. When irradiated B6 x CBAF1 mice were infused with T and NK cell-depleted B6 bone marrow cells and 3 to 30 x 106 B6 spleen cells uniformly lethal GVHD was observed. However, B6 x CBAF1 recipients of T and NK-depleted B6 bone marrow cells and similar numbers of Leu-Leu-OMe-treated B6 spleen cells demonstrated 90 to 100% long term survival. In contrast, Leu-Leu-OMe treatment of B6 donor cells had no beneficial effect on mortality rates in irradiated (B6 x B6-C-H-2bm12)F1 (B6 x bm12F1) recipients. When B6 spleen cells were stimulated in vivo or in vitro with either B6 x CBAF1 or B6 x bm12F1 stimulator cells, the capacity to generate alloantigen-specific CTL was abolished comparably by Leu-Leu-OMe treatment. Thus, the dramatic difference between the effects of Leu-Leu-OMe treatment of B6 spleen cells on the course of GVHD in B6 x CBAF1 and class II MHC only disparate B6 x bm12F1 recipients could not be explained by unique resistance of bm 12-specific CTL precursors to Leu-Leu-OMe. These findings indicate that T cell effector mechanisms distinct from classic cell-mediated cytotoxicity are sufficient to generate lethal GVHD in class II MHC only disparate B6 → B6 x bm12F1 mice.

Original languageEnglish (US)
Pages (from-to)3377-3382
Number of pages6
JournalJournal of Immunology
Volume141
Issue number10
StatePublished - 1988

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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