Deletion of CD98 heavy chain in T cells results in cardiac allograft acceptance by increasing regulatory T cells

Transplantation
Zhong LiuXiao-Kang Li

Abstract

Little is known about the CD98 heavy chain (CD98hc) in the T lymphocyte-mediated immune response to alloantigen. We used an in vitro mixed leukocyte reaction assay and a cardiac transplantation model to evaluate the mechanisms of CD98hc in regulating alloimmune responses. 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. Taken together, our data indic...Continue Reading

References

Feb 9, 1996·Cell·D A Lauffenburger, A F Horwitz
Apr 4, 2006·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Jonathan D Powell

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Citations

Feb 5, 2014·Biochemical and Biophysical Research Communications·Zaied Ahmed BhuyanKoji Yasutomo
Dec 3, 2014·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Jiangang HouXiao-Kang Li
Mar 3, 2017·Cell Death & Disease·Wenkai RenYulong Yin
Apr 3, 2021·Transplantation·Danh T TranSatish N Nadig

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