Then, we investigated the immunosuppressive effect of TGF-β1 gene-modified MSCs on lymphocytes in vitro and its preventive and therapeutical effects on murine aGVHD model in vivo.
Patient's TGFβ1-codon 10 and 25 high/intermediate producers showed a lower incidence of acute GVHD though it did not achieve statistical significance (p = 0.065) on account of the low frequency of this genotype in our patients and donors (11.4 and 8.2% respectively).
In the combined cohort, multivariate analysis confirmed that donors with the TGFβ1-509 T/T genotype also conferred protection against the risk of aGVHD and grades II-IV aGVHD.
TGF-beta1 seems to be an additional regulator of donor engraftment; its low levels probably being one of the factors contributing to the development of acute GVHD.
Genetic background of TGF-beta1 may be involved in aGVHD development and/or severity in the patients who received Bone Marrow Transplantation (BMT) from their siblings with the similar HLA among the Iranian population.
In conclusion, genetic backgrounds of TGF-beta1 and TGF-beta1 RII may be involved in the development of aGVHD in HLA-matched sibling BMT in Japanese children.