[2019 Fall Life Sciences & IBB Seminar]
▶Subject: Pathogenic Function of Bystander CD4 T cells in Autoimmune Encephalomyelitis
▶Speaker: Prof. Je-Min Choi (HanyangUniversity)
▶Date: 4:30PM/Nov. 29(Fri.)/2019
▶Place: Auditorium(1F), Postech Biotech Center
Multiple Sclerosis has been recognized as autoimmune disease mainly induced by myelin-specific T cells. T cells generate antigen-specific immune responses to their cognate antigen as a hallmark of adaptive immunity. Despite the importance of antigen-specific T cell functions, here we introduce that antigen non-related, bystander-activated CD4+ T cells has significant pathogenic roles in experimental autoimmune encephalomyelitis. We, at first, screened inflammatory cytokines which are able to activate T cells without TcRstimulation. Transcriptome analysis demonstrates that interleukin (IL)-1β-and IL-23-prime polyclonal memory phenotype T cells without TcRstimulation express pathogenic TΗ17 signature genes such as RORγt, CCR6, and granulocyte macrophage colony-stimulating factor (GM-CSF). Importantly, when co-transferred with myelin-specific 2D2 TCR-transgenic naive T cells, unrelated OT-II TCR-transgenic memory-like TH17 cells infiltrate the spinal cord and produce IL-17A, interferon (IFN)-γ, and GM-CSF, increasing the susceptibility of the recipients to experimental autoimmune encephalomyelitis in an IL-1 receptor-dependent manner. In humans, IL-1R1high memory CD4+ T cells are major producers of IL-17A and IFN-γ in response to IL-1β and IL-23 independent of TcRstimulation. Collectively, our findings reveal the innate-like pathogenic function of antigen non-related effector/memory CD4+ T cells which would support to explain pathogenic mechanism of autoimmune disease that would be an important alternative target to treat multiple sclerosis.
▶Inquiry: Prof. Yoontae Lee (279-2354)