title: Mast cells suppress murine GVHD in a mechanism independent of CD4+CD25+ regulatory T cells.
abstract: To investigate the role of mast cells in hematopoietic cell transplantation, we assessed graft-versus-host disease (GVHD) in C57BL/6-Kit(W-sh/W-sh) recipients, which virtually lack mast cells, compared with C57BL/6 WT recipients. GVHD was severely exacerbated in C57BL/6-Kit(W-sh/W-sh) mice (median survival time = 13 vs 60 days in wild-type [WT] mice; P < .0001). The increased mortality risk in C57BL/6-Kit(W-sh/W-sh) hosts correlated with increased T-cell numbers in lymph nodes, liver, and gastrointestinal tract sites, as indicated by bioluminescence imaging (P < .001). We did not detect any deficit in the number or function of CD4(+)CD25(+) regulatory T cells (Tregs) in C57BL/6-Kit(W-sh/W-sh) mice. Furthermore, Tregs were equally effective at reducing GVHD in C57BL/6-Kit(W-sh/W-sh) recipients compared with WT recipients containing mast cells. Furthermore, we found that survival of C57BL/6-Kit(W-sh/W-sh) mice during GVHD was significantly improved if the mice were engrafted with bone marrow-derived cultured mast cells from WT C57BL/6 mice but not from interleukin (IL)-10-deficient C57BL/6 mice. These data indicate that the presence of mast cells can significantly reduce GVHD independently of Tregs, by decreasing conventional T-cell proliferation in a mechanism involving IL-10. These experiments support the conclusion that mast cells can mediate a novel immunoregulatory role during hematopoietic cell transplantation.
authors.affiliation: School of Medicine, Division of Bone Marrow Transplant, and.
authors.forename: Dennis B
authors.initials: DB
authors.lastname: Leveson-Gower
authors.forename: Emanuela I
authors.initials: EI
authors.lastname: Sega
authors.forename: Janet
authors.initials: J
authors.lastname: Kalesnikoff
authors.forename: Mareike
authors.initials: M
authors.lastname: Florek
authors.forename: Yuqiong
authors.initials: Y
authors.lastname: Pan
authors.forename: Antonio
authors.initials: A
authors.lastname: Pierini
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Galli
authors.forename: Robert S
authors.initials: RS
authors.lastname: Negrin
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019009:Proto-Oncogene Proteins c-kit / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000276:immunology*
chemical_list: C556062:IL10 protein, mouse; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10; D019009:Proto-Oncogene Proteins c-kit
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