| First Author | Lee HG | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 709 |
| PubMed ID | 30755603 | Mgi Jnum | J:274015 |
| Mgi Id | MGI:6286946 | Doi | 10.1038/s41467-019-08482-w |
| Citation | Lee HG, et al. (2019) Pathogenic function of bystander-activated memory-like CD4(+) T cells in autoimmune encephalomyelitis. Nat Commun 10(1):709 |
| abstractText | T cells generate antigen-specific immune responses to their cognate antigen as a hallmark of adaptive immunity. Despite the importance of antigen-specific T cells, here we show that antigen non-related, bystander memory-like CD4(+) T cells also significantly contribute to autoimmune pathogenesis. Transcriptome analysis demonstrates that interleukin (IL)-1beta- and IL-23-prime T cells that express pathogenic TEta17 signature genes such as RORgammat, 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)-gamma, and GM-CSF, increasing the susceptibility of the recipients to experimental autoimmune encephalomyelitis in an IL-1 receptor-dependent manner. In humans, IL-1R1(high) memory CD4(+) T cells are major producers of IL-17A and IFN-gamma in response to IL-1beta and IL-23. Collectively, our findings reveal the innate-like pathogenic function of antigen non-related memory CD4(+) T cells, which contributes to the development of autoimmune diseases. |
