The T cell response to interleukin 10 alters cellular dynamics and paradoxically promotes CNS autoimmunity (123.16)
| Autor: | Terrence Geiger, Xin Liu, Rajshekhar Alli, Meredith Steeves, Phuong Nguyen, Peter Vogel |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 188:123.16-123.16 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.188.supp.123.16 |
| Popis: | IL10 is a critical anti-inflammatory cytokine, deficiency of which leads to spontaneous autoimmunity. Yet therapeutically administered or ectopically expressed IL10 may either suppress or promote autoimmunity. Distinct lineage-specific activities may explain these contradictory effects. To dissect the T cell-specific response to IL10 during organ-specific autoimmunity, we generated mice with a specific deletion of IL10Rα in T cells and analyzed its impact in experimental allergic encephalomyelitis (EAE). Surprisingly, the T-cell response to IL10 increased EAE severity. This did not result from altered T cell functional potential; T cell cytokine profile and migratory capacity were preserved. IL10 diminished the proliferation of T cells in situ, both at the site of induction and within the target organ, actions that should restrain disease. However, this decreased proliferation was not associated with diminished cell numbers. IL10 acted cell autonomously to sustain the autoreactive T cells essential for immunopathogenesis, promoting their accumulation and distorting the regulatory and effector T cell balance. Therefore T cell specific actions of IL10 can support autoimmune inflammation, and this appears to result from an overall increase in the long term fitness of pathologic T cells. Lineage-restricted, disease-promoting activities of IL10 should be considered in its therapeutic application. |
| Databáze: | OpenAIRE |
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