期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 40, 期 2, 页码 378-387出版社
WILEY
DOI: 10.1002/eji.200939399
关键词
Cell activation; Cell surface molecules; Co-stimulation; Rheumatoid arthritis; T cells
类别
资金
- Royal Swedish Academy of Sciences
- Tobias Foundation
- Cancer Society in Stockholm
- Swedish Children Cancer Foundation
- Swedish Rheumatism association
- King Gustav V 80-year foundation
- Karolinska Institutet foundation
- Swedish Research Council
- Bernard Osher Initiative for Research on Severe Asthma at the Karolinska Institutet
Effector T-cell responses can be modulated by competing positive or negative signals transduced by NK-cell receptors (NKR). In the CD4(+) T-cell population, the expression of NKR is primarily found in the CD4(+)CD28(-) T-cell subset, also known as CD28(null) T cells. These T cells are frequently found in rheumatoid arthritis (RA) and other inflammatory disorders, suggesting that signaling through NKR may play a role in the autoimmune reaction. Here we aimed to dissect the phenotype and function of NKR-expressing CD4(+) CD28(-) T cells in patients with RA. By analyzing a broad array of NKR on CD4(+)CD28(-) T cells we found a significant expression of the co-activating receptors 2B4 (CD244), DNAM-1 (CD226), and CRACC. Pair-wise ligations of 2B4 with DNAM-1 and/or NKG2D lead to increased effector functions of primary CD4(+)CD28(-) T cells to suboptimal levels of anti-CD3 stimulation. Using multi-parameter flow cytometry, we demonstrate that such coligation led to an increased magnitude in overall responsiveness without changing qualitative aspects of the response. Altogether these results demonstrate a pattern of additive effects in NKR-mediated functional modulation of CD4(+)CD28(-) T cells in RA. This may have consequences for the inflammatory responses imposed by these cells, thus influencing disease manifestations.
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