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CD28-dependent differentiation into the effector/memory phenotype is essential for induction of arthritis in interleukin-1 receptor antagonist-deficient mice.

CD28-dependent differentiation into the effector/memory phenotype is essential for induction of arthritis in interleukin-1 receptor antagonist-deficient mice.

Authors :
Kotani M
Hirata K
Ogawa S
Habiro K
Ishida Y
Tanuma S
Horai R
Iwakura Y
Kishimoto H
Abe R
Source :
Arthritis and rheumatism [Arthritis Rheum] 2006 Feb; Vol. 54 (2), pp. 473-81.
Publication Year :
2006

Abstract

Objective: Interleukin-1 receptor antagonist (IL-1Ra)-deficient mice on a BALB/c background spontaneously develop a chronic inflammatory polyarthropathy closely resembling that of rheumatoid arthritis in humans. To elucidate the role of CD28 costimulatory signals in the development of this disease, we studied IL-1Ra/CD28-double-deficient mice.<br />Methods: We crossed IL-1Ra-deficient mice with CD28-deficient mice and observed the incidence and severity of arthritis. To investigate functions of IL-1Ra/CD28-double-deficient T cells, cells were stimulated with CD3 monoclonal antibody or allogeneic antigen-presenting cells (APCs) and their proliferative responses and levels of cytokine production were measured.<br />Results: Disease severity was lower in IL-1Ra/CD28-double-deficient mice than in mice that were deficient only in IL-1Ra, although incidence of arthritis was not affected by the presence or absence of CD28. When pathogenic IL-1Ra-KO T cells were transferred into nude mice, severe arthritis developed. Even though T cells from double-deficient mice showed the same diminished proliferative capacity as was seen in T cells from CD28-single-deficient animals, nude mice into which double-deficient T cells were transferred never developed arthritis.<br />Conclusion: These findings indicate that IL-1Ra/CD28-double-deficient T cells can be activated by IL-1Ra-deficient activated APCs, resulting in induction of arthritis; however, these T cells did not induce the disease under normal conditions, because they did not differentiate into effector/memory phenotype.

Details

Language :
English
ISSN :
0004-3591
Volume :
54
Issue :
2
Database :
MEDLINE
Journal :
Arthritis and rheumatism
Publication Type :
Academic Journal
Accession number :
16453283
Full Text :
https://doi.org/10.1002/art.21769