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- Title
B-Cells Promote Intra-Islet CD8<sup>+</sup> Cytotoxic T-Cell Survival to Enhance Type 1 Diabetes.
- Authors
Brodie, Gillian M.; Wallberg, Maja; Santamaria, Pere; Wong, F. Susan; Green, E. Allison
- Abstract
OBJECTIVE--To determine the role of B-cells in promoting CD8[sup +] T-cell--mediated β cell destruction in chronically inflamed islets. RESEARCH DESIGN AND METHODS--RIP-TNFα-NOD mice were crossed to B-cell-deficient NOD mice, and diabetes development was monitored. We used in vitro antigen presentation assays and in vivo administration of bromodeoxyuridine coupled to flow cytometry assays to assess intra-islet T-cell activation in the absence or presence of B-cells. CD4[sup +]Foxp3[sup +] activity in the absence or presence of B-cells was tested using in vivo depletion techniques. Cytokine production and apoptosis assays determined the capacity of CD8[sup +] T-cells transform to cytotoxic T-lymphocytes (CTLs) and survive within inflamed islets in the absence or presence of B-cells. RESULTS--B-cell deficiency significantly delayed diabetes development in chronically inflamed islets. Reintroduction of B-cells incapable of secreting immunoglobulin restored diabetes development. Both CD4[sup +] and CD8[sup +] T-cell activation was unimpaired by B-cell deficiency, and delayed disease was not due to CD4[sup +]Foxp3[sup +] T-cell suppression of T-cell responses. Instead, at the CTL transition stage, B-cell deficiency resulted in apoptosis of intra-islet CTLs. CONCLUSIONS--In inflamed islets, B-cells are central for the efficient intra-islet survival of CTLs, thereby promoting type 1 diabetes development.
- Publication
Diabetes, 2008, Vol 57, Issue 4, p909
- ISSN
0012-1797
- Publication type
Academic Journal
- DOI
10.2337/db07-1256