To inhibit the immune inflammation in the allografts can be beneficial to organ transplantation. This study aims to induce the donor antigen specific regulatory T cells (Treg cell) inhibit the immune inflammation in the allograft heart. In this study, peripheral exosomes were purified from the mouse serum. A heart transplantation mouse model was developed. The immune inflammation of the allograft heart was assessed by histology and flow cytometry. The results showed that the donor antigen-specific T helper (Th)2 pattern inflammation was observed in the allograft hearts; the inflammation was inhibited by immunizing the recipient mice with the donor-derived exosomes. Purified peripheral exosomes contained integrin MMP1a; the latter induced CD4+ T cells to express Fork head protein-3 and transforming growth factor (TGF)-β via inhibiting the Th2 transcription factor, GATA binding protein 3, in CD4+ T
Mice were transplanted with allograft hearts. The recipient mice were treated as denoted above each column. Exosome: Mice received donor-derived exosomes. #, non-donor-derived exosomes. PAR2-n: The recipient mice are PAR2-deficient mice. (A1-A8) the representative images show the heart histology and the mononuclear cell infiltration (the cells were stained in dark blue) in heart tissue. (B) the mononuclear cells were isolated from the heart tissue and analyzed by flow cytometry. The gated dot plots indicate that the CD4+ CD25+ T cells. (C1-C5) the gated histograms show the frequency of IL-4+ CD4+ T cells. (D) the bars indicate the IL-4 levels in the culture supernatant (by ELISA; the data are presented as mean ± SD. *p < 0.01, compared to the group (C1) the group labels on the Y axis are the same as the histograms of (C1-C8). (E1-E5) the gated histograms show the frequency of IFN-γ+ CD4+ T cells. (F1-F5), the gated histograms show the frequency of proliferating CD4+ T cells after incubating with spleen DCs (DC:T cell = 1:5) and mouse heart extracts (1 μg/ml) for 3 days. Each group consists of 12 mice. Samples from 4 mice were pooled as one sample. The data are representatives of 3 independent experiments.