| First Author | Saxena A | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 6 | Pages | 3140-9 |
| PubMed ID | 22904307 | Mgi Jnum | J:189912 |
| Mgi Id | MGI:5447240 | Doi | 10.4049/jimmunol.1103111 |
| Citation | Saxena A, et al. (2012) Tc17 CD8+ T cells potentiate Th1-mediated autoimmune diabetes in a mouse model. J Immunol 189(6):3140-9 |
| abstractText | An increase in IL-17-producing CD8+ T (Tc17) cells has been reported in the peripheral blood of children with recent onset type 1 diabetes (T1D), but their contribution to disease pathogenesis is still unknown. To directly study the pathogenic potential of beta cell-specific Tc17 cells, we used an experimental model of T1D based on the expression of the neo-self Ag hemagglutinin (HA) in the beta cells of the pancreas. When transferred alone, the IL-17-producing HA-specific CD8+ T cells homed to the pancreatic lymph nodes without causing any pancreatic infiltration or tissue destruction. When transferred together with small numbers of diabetogenic HA-specific CD4+ T cells, a strikingly different phenotype developed. Under these conditions, Tc17 cells sustained disease progression, driving the destruction of beta-islet cells, causing hyperglycemia and ultimately death. Disease progression did not correlate with functional or numerical alterations among the HA-specific CD4+ T cells. Rather, the transferred CD8+ T cells accumulated in the pancreatic islets and a considerable fraction converted, under the control of IL-12, to an IFN-gamma-producing phenotype. Our data indicate that Tc17 cells are not diabetogenic but can potentiate a Th1-mediated disease. Plasticity of the Tc17 lineage is associated with transition to overt disease in this experimental model of T1D. |
