| First Author | Gurlo T | Year | 1999 |
| Journal | J Immunol | Volume | 163 |
| Issue | 11 | Pages | 5770-80 |
| PubMed ID | 10570259 | Mgi Jnum | J:58664 |
| Mgi Id | MGI:1349326 | Doi | 10.4049/jimmunol.163.11.5770 |
| Citation | Gurlo T, et al. (1999) Role of inflammatory infiltrate in activation and effector function of cloned islet reactive nonobese diabetic CD8+ T cells: involvement of a nitric oxide-dependent pathway. J Immunol 163(11):5770-80 |
| abstractText | To investigate how CD8+ T cells interact with beta cells and local inflammatory cells in islets, we have isolated CD8+ T cell clones from nonobese diabetic (NOD) spleen that recognize and destroy both islets and the NOD insulinoma cell line NIT-1. The clones destroyed NOD islets with pre-existing inflammation better than islets without signs of inflammation. Islets from NOD-scid mice were destroyed only poorly, but that could be improved by adding IL-7 to the assay. Anti-IFN-gamma Abs inhibited destruction of infiltrated islets. Single islets were effective stimulators of IFN-gamma production by cloned CD8+ T cells, which varied >50-fold depending on the degree of islet infiltration. This effect of the islet mononuclear infiltrate could be mimicked by adding spleen cells to NIT-1 cells, which augmented IFN-gamma production above the level stimulated by NIT-1 cells alone. The enhancing effect of spleen cells could be attributed to their macrophage subpopulation and was not MHC restricted, although recognition of islet Ag by cloned CD8+ T cells and subsequent islet destruction was restricted to islets expressing H-2Db molecules. An inhibitor of inducible NO synthase inhibited destruction of inflamed islets by cloned CD8+ T cells. We propose that macrophages in inflamed islets provide a form of bystander costimulation of beta cell-specific CD8+ T cells. CD8+ T cells respond to Ag and costimulation by producing IFN-gamma that activates macrophages. Activated macrophages facilitate islet destruction by CD8+ T cells through a NO synthesis-dependent pathway. |
