| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Wu, Tao Wang, Miao Shen, Christine Deng, Ruishu Zeng, Defu Johnston, Heather Siswanto, Kathleen Racine, Jeremy Zhang, Mingfeng |
| Description |
Author Affiliation: Wang M ( Department of Diabetes Research, Beckman Research Institute of City of Hope, Duarte, CA 91010); Racine J ( Department of Diabetes Research, Beckman Research Institute of City of Hope, Duarte, CA 91010); Zhang M ( Department of Diabetes Research, Beckman Research Institute of City of Hope, Duarte, CA 91010); Wu T ( Department of Diabetes Research, Beckman Research Institute of City of Hope, Duarte, CA 91010); Deng R ( Department of Diabetes Research, Beckman Research Institute of City of Hope, Duarte, CA 91010); Johnston H ( Department of Diabetes Research, Beckman Research Institute of City of Hope, Duarte, CA 91010); Shen C ( Eugene and Ruth Roberts Summer Student Academy of City of Hope, Duarte, CA 91010.); Siswanto K ( Eugene and Ruth Roberts Summer Student Academy of City of Hope, Duarte, CA 91010.); Zeng D ( Department of Diabetes Research, Beckman Research Institute of City of Hope, Duarte, CA 91010) |
| Abstract |
In nonautoimmune recipients, induction of mixed and complete chimerism with hematopoietic progenitor cells from MHC (HLA)-matched or -mismatched donors are effective approaches for induction of organ transplantation immune tolerance in both animal models and patients. But it is still unclear whether this is the case in autoimmune recipients. With the autoimmune diabetic NOD mouse model, we report that, although mixed and complete MHC-mismatched chimerism provide immune tolerance to donor-type islet and skin transplants, neither mixed nor complete MHC-matched chimerism does. The MHC-mismatched chimerism not only tolerizes the de novo developed, but also the residual pre-existing host-type T cells in a mismatched MHC class II-dependent manner. In the MHC-mismatched chimeras, the residual host-type peripheral T cells appear to be anergic with upregulation of PD-1 and downregulation of IL-7R . Conversely, in the MHC-matched chimeras, the residual host-type peripheral T cells manifest both alloreactivity and autoreactivity; they not only mediate insulitis and sialitis in the recipient, but also reject allogeneic donor-type islet and skin grafts. Interestingly, transgenic autoreactive BDC2.5 T cells from Rag1(+/+), but not from Rag1(-/-), NOD mice show alloreactivity and mediate both insulitis and rejection of allografts. Taken together, MHC-mismatched, but not MHC-matched, chimerism can effectively provide transplantation immune tolerance in autoimmune recipients. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| Journal |
The Journal of Immunology |
| Issue Number |
4 |
| Volume Number |
193 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2014-08-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Autoimmunity Immunology Diabetes Mellitus Histocompatibility Antigens Class Ii Transplantation Chimera Transplantation Tolerance Allografts Animals Antigens, Cd3 Antigens, Cd8 Cd4-positive T-lymphocytes Graft Rejection Genetics Hematopoietic Stem Cells Homeodomain Proteins Immunologic Memory Insulin Islets Of Langerhans Islets Of Langerhans Transplantation Mice Mice, Inbred Balb C Mice, Inbred C57bl Mice, Inbred Dba Mice, Inbred Nod Organ Transplantation Programmed Cell Death 1 Receptor Biosynthesis Receptors, Interleukin-7 Skin Transplantation Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
