IL-11-stimulated Encephalitogenic CD4+ Cells Induce Aggressive RREAE, Mediated via Th17, CD8+, CD19+ Cells and Neutrophils’ Migration to CNS in Passive Transfer RREAE (P2.407)

Objective: To determine the effector mechanisms of IL-11-induced encephalitogenic CD4 + cells in mediating passive transfer Relapsing Remitting Experimental Autoimmune Encephalomyelitis (RREAE). Background: Our previous studies showed patients with Clinically Isolated Syndrome (CIS) suggestive of MS have increased CSF and serum IL-11 levels. Our human in vitro studies identified that IL-11 induces Th17 cell differentiation and expansion in CIS patients, but not in HCs. Our in vivo RREAE studies confirmed the causative role of IL-11 in worsening disease severity and increasing the number of IL-17 + CD4 + cells within the PBMC, spleen and spinal cord inflammatory infiltrate. Design/Methods: SJL mice were immunized with PLP 139–151 and LN cells harvested on day 11 restimulated with 1) PLP, 2) PLP+IL-11, and 3) PLP+IL-23 for 7 days. Recipient mice received isolated CD4 + cells and sacrificed on day 14, the peak of the first relapse. Results: In vitro antigen recall assay showed IL-11 induced an increase in the number of IL-17 + CD4 + cells in LN and spleen (p + CD4 + cells in spleen (p + IL-17 + CD4 + cells in LN and spleen (p + cells. In passive transfer RREAE induction, injection of IL-11-stimulated CD4 + cells induced severe RREAE, similar to IL-23-stimulated CD4 + cells. Recipient mice of IL-11-stimulated CD4 + cells had higher percentages of IL-17 + CD4 + cells in LNs and CNS infiltrates (both p + cells. Furthermore, IL-11-stimulated CD4 + cells induced higher percentages of CD8 + cells in LN and CNS, as well as neutrophils and CD19 + B cells in the CNS infiltration, indicating the additional effector function of passively transferred IL-11-stimulated CD4 + cells. Conclusions: Our study demonstrated that IL-11 not only induces encephalitogenic Th17 cells, which migrate to the CNS but also induces the migration of neutrophils, CD8 + and B cells to CNS, which may contribute to the chronic CNS inflammatory disease. Study Supported by: The study was supported by R03 AI111592-01 grant from NIH/NINDS. Disclosure: Dr. Kiapour has nothing to disclose. Dr. Kapoor has nothing to disclose. Dr. Zhang has nothing to disclose. Dr. Markovic Plese has received research support from Genzyme.