| First Author | Klocke K | Year | 2017 |
| Journal | Immunology | Volume | 152 |
| Issue | 1 | Pages | 125-137 |
| PubMed ID | 28497863 | Mgi Jnum | J:247189 |
| Mgi Id | MGI:5917863 | Doi | 10.1111/imm.12754 |
| Citation | Klocke K, et al. (2017) CTLA-4 expressed by FOXP3+ regulatory T cells prevents inflammatory tissue attack and not T-cell priming in arthritis. Immunology 152(1):125-137 |
| abstractText | 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+ 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. |
