Constitutive expression of BCL-X(L) in the T lineage attenuates collagen-induced arthritis in Bcl-X(L) 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 (3)H-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.


CONCLUSIONS
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.
Chen
Ying
Y
Vanderbilt University Medical School, Nashville, Tennessee USA.
Rosloniec
Ed
E
Price
Jim
J
Boothby
Mark
M
Chen
Jin
J
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology*; D002453:Cell Cycle / Q000502:physiology; D019070:Cell Lineage / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D008221:Lymphoid Tissue / Q000502:physiology; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D019076:Transgenes / Q000502:physiology; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D007371:Interferon-gamma