1. CD8 Follicular T Cells Promote B Cell Antibody Class Switch in Autoimmune Disease.
- Author
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Valentine KM, Davini D, Lawrence TJ, Mullins GN, Manansala M, Al-Kuhlani M, Pinney JM, Davis JK, Beaudin AE, Sindi SS, Gravano DM, and Hoyer KK
- Subjects
- Animals, Autoimmunity immunology, B-Lymphocytes cytology, B-Lymphocytes immunology, Cell Differentiation immunology, Erythrocytes immunology, Female, Interleukin-2 genetics, Interleukins metabolism, Male, Mice, Mice, Inbred BALB C, Mice, Knockout, Proto-Oncogene Proteins c-bcl-6 metabolism, Receptors, CXCR5 metabolism, Anemia, Hemolytic, Autoimmune immunology, Anemia, Hemolytic, Autoimmune pathology, CD8-Positive T-Lymphocytes immunology, Immunoglobulin Class Switching immunology, T-Lymphocytes, Helper-Inducer immunology
- Abstract
CD8 T cells can play both a protective and pathogenic role in inflammation and autoimmune development. Recent studies have highlighted the ability of CD8 T cells to function as T follicular helper (Tfh) cells in the germinal center in the context of infection. However, whether this phenomenon occurs in autoimmunity and contributes to autoimmune pathogenesis is largely unexplored. In this study, we show that CD8 T cells acquire a CD4 Tfh profile in the absence of functional regulatory T cells in both the IL-2-deficient and scurfy mouse models. Depletion of CD8 T cells mitigates autoimmune pathogenesis in IL-2-deficient mice. CD8 T cells express the B cell follicle-localizing chemokine receptor CXCR5, a principal Tfh transcription factor Bcl6, and the Tfh effector cytokine IL-21. CD8 T cells localize to the B cell follicle, express B cell costimulatory proteins, and promote B cell differentiation and Ab isotype class switching. These data reveal a novel contribution of autoreactive CD8 T cells to autoimmune disease, in part, through CD4 follicular-like differentiation and functionality., (Copyright © 2018 by The American Association of Immunologists, Inc.)
- Published
- 2018
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