Constitutive expression of BCL‐X_L in the T lineage attenuates collagen‐induced arthritis in Bcl‐X_L transgenic mice

Abstract

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 3 H-thymidine incorporation. Apoptosis and cell cycle progression were analyzed by flow cytometry using propidium iodide. Production of CII-specific interferon-␥ (IFN␥), 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 IFN␥ 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 IFN␥ production.

CD4+CD25+ T Cell-Dependent Inhibition of Autoimmunity in Transgenic Mice Overexpressing Human Bcl-2 in T Lymphocytes

“…In agreement with our present study, it has been described recently that the constitutive Tg expression of Bcl-x L in T cells attenuates the development of CIA (42). Although the authors of this study do not clarify the mechanism directly involved in such protective effect, due to the similarities between Bcl-2 and Bcl-x L in the regulation of programmed cell death, and more particularly in the regulation of lymphocyte survival (3,43), it is likely that analogous mechanisms account for the protection against CIA in both Bcl-x L T cell Tg and Bcl-2 Tg2 mice.…”

Overexpression of BclXL in B Cells Promotes Th1 Response and Exacerbates Collagen-Induced Arthritis

“…Interestingly, one earlier study has shown that T cell lineagespecific expression of Bcl-XL transgene resulted in decreased IFN-␥ production and attenuated CIA (33). Several factors may explain the seemingly contradictory results from these two studies.…”

The inflammatory role of phagocyte apoptotic pathways in rheumatic diseases

“…Initial studies in CIA mouse models focused on the overexpression of Bcl2 and Bcl-xL in lymphocytes. Results showed that although overexpression of Bcl-xL in B cells exacerbate CIA 126 , in T cells it attenuates the development of arthritis, potentially through their resistance to apoptosis, delayed cell cycle progression and inhibition of IFN-γ production in response to type II collagen challenge 127 . Similarly, overexpression of Bcl2 in all hematopoietic cells reduces the development of CIA, potentially by resulting in decreased production of antibodies against type II collagen 128 .…”