| First Author | Yi T | Year | 2009 |
| Journal | Blood | Volume | 114 |
| Issue | 14 | Pages | 3101-12 |
| PubMed ID | 19602708 | Mgi Jnum | J:153264 |
| Mgi Id | MGI:4361803 | Doi | 10.1182/blood-2009-05-219402 |
| Citation | Yi T, et al. (2009) Reciprocal differentiation and tissue-specific pathogenesis of Th1, Th2, and Th17 cells in graft-versus-host disease. Blood 114(14):3101-12 |
| abstractText | In acute graft-versus-host disease (GVHD), naive donor CD4(+) T cells recognize alloantigens on host antigen-presenting cells and differentiate into T helper (Th) subsets (Th1, Th2, and Th17 cells), but the role of Th subsets in GVHD pathogenesis is incompletely characterized. Here we report that, in an MHC-mismatched model of C57BL/6 donor to BALB/c recipient, WT donor CD4(+) T cells predominantly differentiated into Th1 cells and preferentially mediated GVHD tissue damage in gut and liver. However, absence of interferon-gamma (IFN-gamma) in CD4(+) T cells resulted in augmented Th2 and Th17 differentiation and exacerbated tissue damage in lung and skin; absence of both IL-4 and IFN-gamma resulted in augmented Th17 differentiation and preferential, although not exclusive, tissue damage in skin; and absence of both IFN-gamma and IL-17 led to further augmentation of Th2 differentiation and idiopathic pneumonia. The tissue-specific GVHD mediated by Th1, Th2, and Th17 cells was in part associated with their tissue-specific migration mediated by differential expression of chemokine receptors. Furthermore, lack of tissue expression of the IFN-gamma-inducible B7-H1 played a critical role in augmenting the Th2-mediated idiopathic pneumonia. These results indicate donor CD4(+) T cells can reciprocally differentiate into Th1, Th2, and Th17 cells that mediate organ-specific GVHD. |
