Constitutive expression of Bcl-xL in the T lineage attenuates collagen-induced arthritis in Bcl-xL transgenic mice

Objective. To determine if inhibition of T cell apoptosis through constitutive expression of Bcl-x(L) in the T lineage influences inflammatory arthritis in the mouse collagen-induced arthritis (CIA) model. Methods. The incidence and severity of arthritis were quantified in Bcl-x(L) 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 H-3-thymidine incorporation. Apoptosis and cell cycle progression were analyzed by flow cytometry using propidium iodide. Production of CII-specific interferon-gamma (IFNgamma), interleukin-5 (IL-5), and IL-10 was determined by enzyme-linked immunosorbent assay. Results. Disease severity in CIA was significantly attenuated in Bcl-x(L) transgenic mice compared with their nontransgenic littermates. Inhibition of CIA was associated with decreased T cell apoptosis, delayed cell cycle progression, and reduced IFNgamma production. Conclusion. Rather than promoting inflammation, inhibition of apoptosis by expression of the Bcl-x(L) protein in the T lineage attenuates disease progression in CIA, probably through inhibition of IFNgamma production.