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CTLA-4 expressed by FOXP3+ regulatory T cells prevents inflammatory tissue attack and not T-cell priming in arthritis.
- Source :
- Immunology; Sep2017, Vol. 152 Issue 1, p125-137, 13p
- Publication Year :
- 2017
-
Abstract
- Cytotoxic T-lymphocyte antigen 4 ( CTLA-4) -mediated regulation of already tolerized autoreactive T cells is critical for understanding autoimmune responses. Although defects in CTLA-4 contribute to abnormal FOXP3<superscript>+</superscript> regulatory T (Treg) cell function in rheumatoid arthritis, its role in autoreactive T cells remains elusive. We studied immunity towards the dominant collagen type II ( CII) T-cell epitope in collagen-induced arthritis both in the heterologous setting and in the autologous setting where CII is mutated at position E266D in mouse cartilage. CTLA-4 regulated all stages of arthritis, including the chronic phase, and affected the priming of autologous but not heterologous CII-reactive T cells. CTLA-4 expression by both conventional T (Tconv) cells and Treg cells was required but while Tconv cell expression was needed to control the priming of naive autoreactive T cells, CTLA-4 on Treg cells prevented the inflammatory tissue attack. This identifies a cell-type-specific time window when CTLA-4-mediated tolerance is most powerful, which has important implications for clinical therapy with immune modulatory drugs. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00192805
- Volume :
- 152
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 124486051
- Full Text :
- https://doi.org/10.1111/imm.12754