| First Author | Racine JJ | Year | 2020 |
| Journal | J Immunol | Volume | 205 |
| Issue | 8 | Pages | 2026-2038 |
| PubMed ID | 32938729 | Mgi Jnum | J:300375 |
| Mgi Id | MGI:6502453 | Doi | 10.4049/jimmunol.2000114 |
| Citation | Racine JJ, et al. (2020) T Cells from NOD-PerIg Mice Target Both Pancreatic and Neuronal Tissue. J Immunol 205(8):2026-2038 |
| abstractText | It has become increasingly appreciated that autoimmune responses against neuronal components play an important role in type 1 diabetes (T1D) pathogenesis. In fact, a large proportion of islet-infiltrating B lymphocytes in the NOD mouse model of T1D produce Abs directed against the neuronal type III intermediate filament protein peripherin. NOD-PerIg mice are a previously developed BCR-transgenic model in which virtually all B lymphocytes express the H and L chain Ig molecules from the intra-islet-derived anti-peripherin-reactive hybridoma H280. NOD-PerIg mice have accelerated T1D development, and PerIg B lymphocytes actively proliferate within islets and expand cognitively interactive pathogenic T cells from a pool of naive precursors. We now report adoptively transferred T cells or whole splenocytes from NOD-PerIg mice expectedly induce T1D in NOD.scid recipients but, depending on the kinetics of disease development, can also elicit a peripheral neuritis (with secondary myositis). This neuritis was predominantly composed of CD4(+) and CD8(+) T cells. Ab depletion studies showed neuritis still developed in the absence of NOD-PerIg CD8(+) T cells but required CD4(+) T cells. Surprisingly, sciatic nerve-infiltrating CD4(+) cells had an expansion of IFN-gamma(-) and TNF-alpha(-) double-negative cells compared with those within both islets and spleen. Nerve and islet-infiltrating CD4(+) T cells also differed by expression patterns of CD95, PD-1, and Tim-3. Further studies found transitory early B lymphocyte depletion delayed T1D onset in a portion of NOD-PerIg mice, allowing them to survive long enough to develop neuritis outside of the transfer setting. Together, this study presents a new model of peripherin-reactive B lymphocyte-dependent autoimmune neuritis. |
