'Indirect' Acute Islet Allograft Destruction in Nonobese Diabetic Mice Is Independent of Donor Major Histocompatibility Complex and Requires Host B Lymphocytes

Autor: Tinalyn Kupfer, K. Pham, Joshua N. Beilke, Jonathan D. Buhrman, Ronald G. Gill
Rok vydání: 2008
Předmět:
Zdroj: Transplantation Proceedings. 40:462-463
ISSN: 0041-1345
DOI: 10.1016/j.transproceed.2008.01.054
Popis: Islet allografts are destroyed rapidly in spontaneously diabetic nonobese diabetic (NOD) mice. However, whether this process is more similar to conventional allograft immunity, islet-specific autoimmune pathogenesis, or both remains controversial. In particular, we sought to determine whether C57BI/6 donor islet major histocompatibility complex (MHC) class I or class II expression was required for islet allograft destruction in autoimmune prone NOD mice versus non-autoimmune–prone BALB/c mice. Results show that islet allografts deficient in both MHC I and II are uniformly accepted in BALB/c mice. In sharp contrast, such MHC-deficient allografts were destroyed acutely in spontaneously diabetic NOD mice. Such donor MHC-independent rejection implicates “indirect” (host MHC-restricted) immunity as a pathway responsible for islet injury. To determine whether host NOD B lymphocytes could contribute to indirect graft recognition, wild-type and MHC I/II–deficient allografts were grafted into B-lymphocyte–deficient (μMT) NOD mice. Whereas wild-type NOD mice could reject MHC-I/II–deficient islet allografts, such grafts were all accepted in B-lymphocyte–deficient NOD mice. Taken together, these results indicate that NOD mice are capable of vigorous donor MHC-independent islet allograft rejection not found in non-autoimmune–prone recipients. Importantly, B lymphocytes may play a key role as antigen-presenting cells in this exuberant host ’indirect’ response found in NOD mice.
Databáze: OpenAIRE