Intermediate TCR cells can induce graft-versus-host disease after allogeneic bone marrow transplantation

Cell Immunol. 1998 Apr 10;185(1):14-29. doi: 10.1006/cimm.1998.1263.

Abstract

Mice fall victim to GVHD when subjected to immunosuppressive treatment and injected with allogeneic bone marrow cells. A major population of cells associated with GVHD is known to be T cells. However, whether such T cells are of thymic or extrathymic origin is obscure. We applied two immunosuppressive conditions, 9 and 6.5 Gy irradiation, to C3H/He mice (H-2k). Bone marrow cells for injection were obtained from C57BL/6 (B6) mice (H-2b). The 9-Gy mice were reconstituted by lymphocytes of donor origin and showed GVHD, whereas 6.5-Gy mice were reconstituted by lymphocytes of recipient origin and showed mild GVHD. The liver was the organ where the reconstitution of lymphocytes occurred efficiently, and a major lymphocyte subset was intermediate (int) CD3 cells (i.e., CD3int cells) in both mice. CD3int cells had the properties of extrathymic T cells, showing the phenotype of NK1.1 + CD3int using invariant V alpha 14 chain. In 6.5-Gy mice, allogeneic cells were rejected by extrathymic T cells of recipient origin. The stored CD3int cells from the liver of 9-Gy mice evoked similar GVHD when transferred into 6.5-Gy irradiated C3H/He mice. These results suggest that CD3int cells of extrathymic origin are a major population for the induction of GVHD under immunosuppressive conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Bone Marrow Cells / immunology
  • Bone Marrow Transplantation / immunology*
  • Bone Marrow Transplantation / pathology
  • CD3 Complex / analysis
  • Cell Movement / immunology
  • Cell Separation
  • Cytotoxicity, Immunologic
  • Flow Cytometry
  • Gamma Rays
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / immunology*
  • Graft vs Host Disease / pathology
  • Immunophenotyping
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / transplantation
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / pathology
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Radiation Chimera
  • Receptors, Antigen, T-Cell / analysis*
  • T-Lymphocyte Subsets / classification
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • Time Factors
  • Transplantation, Homologous

Substances

  • CD3 Complex
  • Receptors, Antigen, T-Cell