CD25+ immunoregulatory T-cells of donor origin suppress alloreactivity after BMT. Biol Blood Marrow Transplant 2002;8(10):525-35
Date
11/19/2002Pubmed ID
12434947DOI
10.1053/bbmt.2002.v8.pm12434947Scopus ID
2-s2.0-0036435911 (requires institutional sign-in at Scopus site) 82 CitationsAbstract
We have previously identified donor-derived Thy1+ alphabeta T-cell receptor (TCR)+ CD4+ CD8- regulatory T-cells that suppress GVH reactivity induced by donor leukocyte infusion (DLI) after BMT. These cells develop in the recipient thymus and may play a role in the maintenance of donor-host tolerance after allogeneic BMT. In the present study, we sought to further characterize the T-cells responsible for the regulatory cell activity in our model. Lethally irradiated recipient AKR mice (H-2k) received transplants of BM from CD25-deficient (-/-) C57BL/6 mice (H-2b). Recipients of CD25-deficient BM developed more severe GVHD after DLI than did recipients of normal BM, a result that indirectly suggests that CD4+ CD25+ regulatory T-cells are important to the suppression of GVH reactivity after allogeneic BMT. GVHD was accompanied by mortality, body weight loss, and elevated percentages of T-cells from the DLI in the peripheral blood in mice that received CD25-deficient BM compared to mice that received normal BM. Both CD40-CD40L and CD28-B7 costimulatory pathways have been implicated in the generation of CD25+ regulatory T-cells. Therefore, we tested whether deficiency in either of these pathways affected the activity of donor BM-derived regulatory T-cells. The absence of CD40L did not affect the regulatory T-cells (ie, recipient mice were still protected from DLI-induced GVHD). In contrast, use of marrow from CD28-deficient mice resulted in complete loss of suppression of GVH reactivity. Thus, CD28 but not CD40L was critical for the generation and/or activation of immunoregulatory T-cells that suppressed GVHD induced by DLI. Together, the results of these experiments suggest that CD4+ CD25+ regulatory T-cells suppress GVH reactivity after BMT and that CD28 expression is indispensable for the generation of these cells.
Author List
Johnson BD, Konkol MC, Truitt RLAuthors
Bryon D. Johnson PhD Adjunct Professor in the Medicine department at Medical College of WisconsinRobert L. Truitt PhD Emeritus Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBone Marrow Transplantation
CD28 Antigens
CD4-Positive T-Lymphocytes
CD40 Ligand
Graft vs Host Disease
Immune Tolerance
Lymphocyte Transfusion
Mice
Mice, Inbred Strains
Mice, Knockout
Receptors, Interleukin-2
Transplantation, Homologous
