Faculty Collaboration Database

Role of immunoregulatory donor T cells in suppression of graft-versus-host disease following donor leukocyte infusion therapy. J Immunol 1999 Dec 15;163(12):6479-87

Date

12/10/1999

Pubmed ID

10586039

Scopus ID

2-s2.0-0032741541 (requires institutional sign-in at Scopus site)   62 Citations

Abstract

In murine models of allogeneic bone marrow transplantation (BMT), MHC-mismatched recipients given a delayed infusion of donor leukocytes (DLI) at 21 days posttransplant develop significant GVHD whereas MHC-matched recipients do not. The current study was initially designed to test the hypothesis that small numbers of T cells in the MHC-mismatched donor bone marrow (BM) graft exacerbated graft-vs-host disease (GVHD) when DLI was administered at 21 days after BMT. Ex vivo depletion of Thy1+ cells from the donor BM had no impact on the severity of GVHD after DLI. However, depletion of donor T cells in vivo with a Thy1 allele-specific mAb given after BMT resulted in significantly more severe GVHD after DLI. Similar results were obtained in a MHC-matched model of allogeneic BMT, indicating that this was a general phenomenon and not model dependent. These results indicated that a population of donor-derived Thy1+ cells suppressed graft-vs-host reactivity after DLI. Results of experiments with thymectomized recipients demonstrated that an intact thymus was required for generation of the immunoregulatory donor cells. Experiments using TCR beta-chain knockout mice as BM donors indicated that the immunosuppressive Thy1+ cells coexpressed alphabetaTCR heterodimers. Similar experiments with CD4 and CD8 knockout donor BM suggested that the immunoregulatory Thy1+alphabetaTCR+ cells consisted of two subpopulations: a CD4+CD8- subpopulation and a CD4-CD8- subpopulation. Together, these results show that thymus-derived, Thy1+alphabetaTCR+ donor cells generated early after allogeneic BMT suppress the graft-vs-host reactivity of T cells given as DLI. These cells may mediate dominant peripheral tolerance after allogeneic BMT.

Author List

Johnson BD, Becker EE, LaBelle JL, Truitt RL

Author

Bryon D. Johnson PhD Adjunct Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antibodies, Monoclonal
CD4 Antigens
CD8 Antigens
Cell Differentiation
Graft vs Host Disease
Histocompatibility Testing
Immunophenotyping
Isoantibodies
Leukocyte Transfusion
Lymphocyte Activation
Lymphocyte Count
Lymphocyte Depletion
Major Histocompatibility Complex
Mice
Mice, Inbred AKR
Mice, Inbred C57BL
Mice, Knockout
Radiation Chimera
Receptors, Antigen, T-Cell, alpha-beta
Spleen
T-Lymphocyte Subsets
T-Lymphocytes, Cytotoxic
T-Lymphocytes, Helper-Inducer
Thy-1 Antigens
Thymus Gland