| Autor: |
Kolar P, Knieke K, Hegel JK, Quandt D, Burmester GR, Hoff H, Brunner-Weinzierl MC |
| Zdroj: |
Arthritis & Rheumatism; Jan2009, Vol. 60 Issue 1, p123-132, 10p |
| Abstrakt: |
OBJECTIVE: CD4+CD25+ regulatory T cells (known as Treg cells) suppress unwanted and autoreactive T cell responses. Treg cells express the costimulatory molecule CTLA-4 intracellularly, but the mechanisms by which Treg cells exploit CTLA-4 signaling remain unclear. The present study was undertaken to investigate the role of CTLA-4 in controlling the homeostasis and suppressive function of Treg cells. METHODS: Murine Treg cells were analyzed by flow cytometry for coexpression of CTLA-4 and typical Treg cell-expressed molecules, and the influence of CTLA-4 on T cell proliferation, suppression, and apoptosis was investigated by in vitro assays. To analyze the importance of CTLA-4 in Treg cell-mediated suppression in vivo, wild-type Treg cells were transferred into CTLA-4-deficient mice displaying lymphoproliferation, and survival was monitored over time. RESULTS: A strong correlation between expression of forkhead box P3 and ex vivo expression of CTLA-4 in Treg cells was observed. Inhibition of CTLA-4 signaling in Treg cells during in vitro stimulation increased cell cycling and led to enhanced activation-induced cell death (AICD), which was mediated by CD95/CD95 ligand-induced activation of caspases. Blockade of CTLA-4 signaling resulted in impairment of the suppressive capacity of Treg cells. Despite these effects, high amounts of Treg cells persisted in CTLA-4-deficient mice. Results of transfer experiments in CTLA-4-deficient mice showed that the mice had a significantly prolonged lifespan when CTLA-4-competent Treg cells were injected. CONCLUSION: Expression of CTLA-4 on Treg cells serves to control T cell proliferation, to confer resistance against AICD, and to maintain the suppressive function of Treg cells. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
Plný text