Pathogenicity of autoreactive Th17 cells is dependent on T-bet expression in non-T-helper cells in experimental autoimmune encephalomyelitis

Tuesday, September 23, 2014 — Poster Session III
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NCI	IMMUNO-8

* FARE Award Winner

Authors

• B. Kwong
• D. McGavern
• V. Lazarevic

Abstract

Experimental autoimmune encephalomyelitis (EAE) is a murine model for multiple sclerosis in which autoreactive CD4+ T-helper cells infiltrate the central nervous system (CNS) and initiate autoimmune inflammation. We have previously shown that EAE induction via the adoptive transfer of CNS antigen-specific Th17 cells requires T-cell-intrinsic expression of the transcription factor T-bet. To assess the potential pathogenic contribution of T-bet expression in non-T-helper cells, we adoptively transferred 2D2 TCR-transgenic Th17 cells on a wild-type background (2D2 WT) into T-bet-deficient (Tbx21-/-) or WT recipient mice. 2D2 WT Th17 cells, while fully pathogenic in WT hosts, showed significantly reduced infiltration into the CNS of Tbx21-/- recipients and were unable to induce EAE in these mice. This impairment in 2D2 WT cell infiltration into the Tbx21-/- CNS was associated with ineffective local re-activation by antigen-presenting cells in the Tbx21-/- CNS. Using T-bet-ZsGreen reporter mice, we confirmed that subsets of dendritic cells within the CNS express T-bet during active EAE, suggesting a critical role for T-bet-expressing DCs in the regulation of autoreactive Th17 cell infiltration. Ongoing studies will seek to identify the pathogenic role of T-bet in DCs and elucidate their interactions with 2D2 Th17 cells in the initiation and progression of EAE.

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