Essential role of T cell NF-kappa B activation in collagen-induced arthritis.

Seetharaman R, Mora AL, Nabozny G, Boothby M, Chen J
J Immunol. 1999 163 (3): 1577-83

PMID: 10415062

NF-kappa B/Rel proteins are ubiquitous transcription factors that are activated by proinflammatory signals or engagement of Ag receptors. To study the role of NF-kappa B/Rel signaling in T lymphocytes during autoimmune disease, we investigated type II collagen-induced arthritis (CIA) in transgenic mice expressing a constitutive inhibitor of NF-kappa B/Rel (I kappa B alpha(Delta N)) in the T lineage. Expression of the I kappa B alpha(Delta N) transgene was persistently high in adult peripheral lymphoid organs and undetectable in T cell-depleted splenocytes, suggesting the expression of the transgene is restricted to the T lineage. The incidence and severity of CIA were decreased significantly in these I kappa B alpha(Delta N) transgenic mice compared with nontransgenic littermates. Inhibition of CIA was not due solely to a decrease in their CD8+ population because transfer of wild-type CD8+ cells into transgenic mice failed to restore disease susceptibility. Protection against disease was associated with a moderate decrease in clonal expansion and a profound and persistent decrease in Ag-induced IFN-gamma production in vivo. Consistent with decreased level of anti-type II collagen-specific Abs and IFN-gamma, serum levels of IgG2a anti-CII Abs were significantly reduced. However, anti-CII-specific IgG1 levels were normal, indicating that some aspects of T cell help were unaffected. Taken together, these results suggest that inhibition of NF-kappa B in T cells impairs CIA development in vivo through decreases in type 1 T cell-dependent responses.

MeSH Terms (23)

Animals Arthritis, Experimental Cattle CD8-Positive T-Lymphocytes Cell Lineage Collagen DNA-Binding Proteins Epitopes, T-Lymphocyte I-kappa B Proteins Immunoglobulin G Incidence Interferon-gamma Lymphocyte Count Lymphoid Tissue Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Transgenic NF-kappa B NF-KappaB Inhibitor alpha Severity of Illness Index T-Lymphocytes Transgenes

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