| First Author | Liu Z | Year | 2012 |
| Journal | Transplantation | Volume | 93 |
| Issue | 11 | Pages | 1116-24 |
| PubMed ID | 22588539 | Mgi Jnum | J:283959 |
| Mgi Id | MGI:6378087 | Doi | 10.1097/TP.0b013e31824fd7cd |
| Citation | Liu Z, et al. (2012) Deletion of CD98 heavy chain in T cells results in cardiac allograft acceptance by increasing regulatory T cells. Transplantation 93(11):1116-24 |
| abstractText | BACKGROUND: Little is known about the CD98 heavy chain (CD98hc) in the T lymphocyte-mediated immune response to alloantigen. METHODS: We used an in vitro mixed leukocyte reaction assay and a cardiac transplantation model to evaluate the mechanisms of CD98hc in regulating alloimmune responses. RESULTS: A T cell-specific deficiency of CD98hc resulted in lower responses to alloantigen stimulation in a mixed leukocyte reaction assay, and CD98hc-deficient mice accepted full major histocompatibility complex-mismatched cardiac allografts. Consistent with graft survival, the infiltration of the graft by immune cells in CD98hc-deficient mice was significantly lower than that in wild-type mice. A chemotaxis assay revealed the migration of CD98hc-deficient lymphocytes to decrease in the presence of CCL5 compared with wild-type cells. Moreover, the proportion of CD4/Foxp3-positive cells and Foxp3 messenger RNA increased significantly in CD98hc-deficient recipients, consistent with the down-regulation of mammalian target of rapamycin and PS6 kinase; and allograft permanent acceptance was shortened by the depletion of antibody-induced regulatory T cells. Finally, neutralizing antibody against CD98hc prolonged the cardiac allograft survival. CONCLUSIONS: Taken together, our data indicate that T cell-specific deficiency in CD98hc can contribute to cardiac allograft permanent acceptance correlating with the attenuation of lymphocyte migration and by increasing the generation of regulatory T cells. These findings are expected to make it possible to develop novel approaches for treating allograft rejection and promoting transplantation tolerance. |
