Pathogenic function of bystander-activated memory-like CD4+ T cells in autoimmune encephalomyelitis

• Published in: Nature communications Vol. 10; no. 1; p. 709
• Main Authors: Lee, Hong-Gyun, Lee, Jae-Ung, Kim, Do-Hyun, Lim, Sangho, Kang, Insoo, Choi, Je-Min
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.02.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 14/63; 38/88; 38/90; 38/91; 631/250/1619/554/1898; 631/250/2152/1566/1571; 631/250/38; 64/110; 64/60; 96/1; 96/21; 96/31; 96/34; Adaptive Immunity; Animals; Antigens; Autoimmune diseases; CCR6 protein; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Colony-stimulating factor; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - metabolism; Encephalomyelitis, Autoimmune, Experimental - pathology; Experimental allergic encephalomyelitis; Female; Gene expression; Granulocyte-macrophage colony-stimulating factor; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Helper cells; Humanities and Social Sciences; Humans; IL-1β; Immunity; Immunological memory; Interferon; Interferon-gamma - metabolism; Interleukin 1; Interleukin 1 receptors; Interleukin 23; Interleukins - immunology; Interleukins - metabolism; Lymphocytes; Lymphocytes T; Male; Memory cells; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; multidisciplinary; Myelin; Nuclear Receptor Subfamily 1, Group F, Member 3 - genetics; Pathogenesis; Receptors, CCR6 - genetics; Receptors, Interleukin-1 - metabolism; Science; Science (multidisciplinary); Spinal cord; Spinal Cord - immunology; Spinal Cord - pathology; T cell receptors; Th17 Cells - immunology; Th17 Cells - metabolism; γ-Interferon
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-08482-w

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)-1β- and IL-23-prime T cells that express pathogenic T Η 17 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 T H 17 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-1R1 high memory CD4 + T cells are major producers of IL-17A and IFN-γ in response to IL-1β 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. T cells express specific T cell receptors (TCR) to recognise antigens and initiate adaptive immune responses. Here the authors show, in a mouse model of autoimmune encephalomyelitis, that memory-like CD4 T cells expressing unrelated TCR can also infiltrate the spinal cord and contribute to autoimmunity.