| Autor: |
Jeremy J, Racine, Harold D, Chapman, Rosalinda, Doty, Brynn M, Cairns, Timothy J, Hines, Abigail L D, Tadenev, Laura C, Anderson, Torrian, Green, Meaghan E, Dyer, Janine M, Wotton, Zoë, Bichler, Jacqueline K, White, Rachel, Ettinger, Robert W, Burgess, David V, Serreze |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
J Immunol |
| ISSN: |
1550-6606 |
| Popis: |
It has become increasingly appreciated that autoimmune responses against neuronal components play an important role in type 1 diabetes (T1D(4)) pathogenesis. In fact, a large proportion of islet-infiltrating B-lymphocytes in the NOD mouse model of T1D produce antibodies 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 heavy and light chain immunoglobulin 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 naïve 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. Antibody 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-γ(−) and TNF-α(−) double negative cells compared to 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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