Constitutive expression of BCL-XL in the T lineage attenuates collagen-induced arthritis in Bcl-XL transgenic mice
Article first published online: 5 FEB 2002
Copyright © 2002 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 46, Issue 2, pages 514–521, February 2002
How to Cite
Chen, Y., Rosloniec, E., Price, J., Boothby, M. and Chen, J. (2002), Constitutive expression of BCL-XL in the T lineage attenuates collagen-induced arthritis in Bcl-XL transgenic mice. Arthritis & Rheumatism, 46: 514–521. doi: 10.1002/art.10128
- Issue published online: 5 FEB 2002
- Article first published online: 5 FEB 2002
- Manuscript Accepted: 24 SEP 2001
- Manuscript Received: 18 JUN 2001
- Vanderbilt-Ingram Cancer Center
- Diabetes Research and Training Center
- American Heart Association grant. Grant Number: 97300889N
- ACS institutional research. Grant Number: IN-25-38
- Boehringer Ingelheim Pharmaceutical Inc.
- NIH grants. Grant Numbers: R01-HD-36400, R01-GM-42550, R01-HL-61752
To determine if inhibition of T cell apoptosis through constitutive expression of Bcl-XL in the T lineage influences inflammatory arthritis in the mouse collagen-induced arthritis (CIA) model.
The incidence and severity of arthritis were quantified in Bcl-XL transgenic mice and nontransgenic littermates after immunization with type II collagen (CII). To correlate T cell responses with disease phenotype, antigen-specific T cell proliferation was measured by 3H-thymidine incorporation. Apoptosis and cell cycle progression were analyzed by flow cytometry using propidium iodide. Production of CII-specific interferon-γ (IFNγ), interleukin-5 (IL-5), and IL-10 was determined by enzyme-linked immunosorbent assay.
Disease severity in CIA was significantly attenuated in Bcl-XL transgenic mice compared with their nontransgenic littermates. Inhibition of CIA was associated with decreased T cell apoptosis, delayed cell cycle progression, and reduced IFNγ production.
Rather than promoting inflammation, inhibition of apoptosis by expression of the Bcl-XL protein in the T lineage attenuates disease progression in CIA, probably through inhibition of IFNγ production.