Absence of β2 integrins impairs regulatory T cells and exacerbates CD4+ T cell-dependent autoimmune carditis

The immunopathogenic mechanisms mediating inflammation in multiorgan autoimmune diseases may vary between the different target tissues. We used the K/BxN TCR transgenic mouse model to investigate the contribution of CD4(+) T cells and β(2) integrins in the pathogenesis of autoimmune arthritis and en...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2011-09, Vol.187 (5), p.2702-2710
Main Authors: Haasken, Stefanie, Auger, Jennifer L, Binstadt, Bryce A
Format: Article
Language:English
Subjects:
Animals
Arthritis, Experimental - immunology
Arthritis, Experimental - pathology
Autoimmune Diseases - immunology
Autoimmune Diseases - pathology
CD18 Antigens - immunology
CD4-Positive T-Lymphocytes - immunology
Cell Separation
Flow Cytometry
Fluorescent Antibody Technique
Immunohistochemistry
Mice
Mice, Inbred C57BL
Mice, Transgenic
Myocarditis - immunology
Myocarditis - pathology
T-Lymphocytes, Regulatory - immunology
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Summary:The immunopathogenic mechanisms mediating inflammation in multiorgan autoimmune diseases may vary between the different target tissues. We used the K/BxN TCR transgenic mouse model to investigate the contribution of CD4(+) T cells and β(2) integrins in the pathogenesis of autoimmune arthritis and endocarditis. Depletion of CD4(+) T cells following the onset of arthritis specifically prevented the development of cardiac valve inflammation. Genetic absence of β(2) integrins had no effect on the severity of arthritis and unexpectedly increased the extent of cardiovascular pathology. The exaggerated cardiac phenotype of the β(2) integrin-deficient K/BxN mice was accompanied by immune hyperactivation and was linked to a defect in regulatory T cells. These findings are consistent with a model in which the development of arthritis in K/BxN mice relies primarily on autoantibodies, whereas endocarditis depends on an additional contribution of effector T cells. Furthermore, strategies targeting β(2) integrins for the treatment of systemic autoimmune conditions need to consider not only the role of these molecules in leukocyte recruitment to sites of inflammation, but also their impact on the regulation of immunological tolerance.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1000967