suppress murine GVHD in a mechanism independent of CD 4 + CD 25 + regulatory T cells
نویسندگان
چکیده
To investigate the role of mast cells in hematopoietic cell transplantation, we assessed graft vs. host disease (GVHD) in C57BL/6-Kit recipients, which virtually lack mast cells, as compared to C57BL/6 WT recipients. GVHD was severely exacerbated in C57BL/6-Kit mice (median survival time, MST = 13 days vs. 60 days in WT mice; p<0.0001). The increased mortality risk in C57BL/6-Kit hosts correlated with increased T cell numbers in lymph nodes, liver, and gastrointestinal tract sites, as indicated by bioluminescence imaging (BLI; p < 0.001). We did not detect any deficit in the number or function of CD4CD25 regulatory T cell (Treg) in C57BL/6-Kit mice. Furthermore, Treg were equally effective at reducing GVHD in C57BL/6-Kit recipients as compared to WT recipients containing mast cells. Further, we found that survival of C57BL/6-Kit mice during GVHD was significantly improved if the mice were engrafted with bone marrow-derived cultured mast cells (BMCMCs) from WT C57BL/6 mice but not from IL-10-deficient C57BL/6 mice. These data indicate that the presence of mast cells can significantly reduce GVHD independently of Treg, by decreasing Tcon 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. For personal use only. on July 14, 2017. by guest www.bloodjournal.org From
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CD4 CD25 T cells have been implicated in two apparently opposing functions, namely an activated effector function but also a regulatory function. In human hematopoietic stem cell transplantation (HSCT), the frequency of CD4CD25 T cells is increased and this increase was reported to correlate with graft-versus-host disease (GvHD), suggesting that the effector function predominates. In mice, CD4C...
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