Intestinal graft-versus-host disease is initiated by donor T cells distinct from classic cytotoxic T lymphocytes

Dwain L Thiele, M. L. Eigenbrodt, S. E. Bryde, E. H. Eigenbrodt, P. E. Lipsky

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

In these studies, the role of T helper and T cytotoxic cells in generating intestinal graft-vs.-host disease (GVHD) was examined. Treatment of C57BL/6J (B6) splenocytes with L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) selectively removes natural killer cells, cytotoxic T lymphocyte (CTL) precursors, and the capacity to cause lethal GVHD in irradiated B6xDBA/2 F1 (B6D2F1) mice while preserving T helper cell function. Neither control nor Leu-Leu-OMe-treated DBA/2 donor spleen and bone marrow cells were found to induce lethal GVHD in B6D2F1 recipients. However, extensive colonic GVHD developed in B6D2F1 recipients of DBA/2 bone marrow and spleen cells. Enteropathic GVHD in DBA/2 → B6D2F1 mice was reduced in severity after anti-L3T4 + C treatment of donor cells, and was eliminated by anti-Thy1.2 + C or the combination of anti-L3T4 and anti-Lyt2 + C treatment of the donor cell inoculum. However, neither anti-Lyt2 + C, Leu-Leu-OMe, nor anti-Lyt2 + C and Leu-Leu-OMe treatment of donor cells significantly decreased severity of gut GVHD. Leu-Leu-OMe treatment of DBA/2 or B6 SpC was comparably effective in preventing in vitro in vivo generation of B6D2F1-specific CTL. These findings, therefore, demonstrate that histologically severe enteropathic GVHD does not require participation of CTL and is not always associated with high mortality rates.

Original languageEnglish (US)
Pages (from-to)1947-1956
Number of pages10
JournalJournal of Clinical Investigation
Volume84
Issue number6
DOIs
StatePublished - 1989

ASJC Scopus subject areas

  • Medicine(all)

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