Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
We found in reproducible experiments in which the mice not prone to autoimmune disease were immunized repeatedly with antigen that overstimulation of CD4 T cells led to the development of aiCD4 T cell which had undergone TCR revision capable of inducing varieties of autoantibody and antigen-specific CTL via antigen cross-presentation, after which they caused SLE (Tsumiyama K et al., 2009). Here we identify aiCD4 T cell as DOCK8+CD4 T cell.
aiCD4 T cell was searched by transferring different fractions of CD4 T cells of x12 OVA-immunized BALB/c female mice into naïve mice and tested if autoantibodies were raised, mass spectrometry, and FACS.
We focused CD45RBlo CD122lo PD-1+CD4 T cell as aiCD4 T candidate, and its membrane uniquely expressed DOCK8. DOCK8+CD4 T cell was a large lymphocyte with abundant ER and mitochondria, ICOS+ CXCR5- PD1+ Ly6C+ LFA1+, produced increased IFNg, IL-4, IL-6, IL-17 and IL-21, and its TCR repertoire was deviated. Upon transfer to naïve mice or to the x8 OVA-pre-immunized and CD4 T-depleted mice in which CTL was yet immature, DOCK8+CD4 T cells induced SLE, where anti-dsDNA/ Sm Ab, glomerulonephritis of WHO IV/V types (Table, upper), skin liquefaction degeneration, splenic periarteriolar fibrosis with amyloid-like deposits classical of Onion-skin lesion, pericholangitis, pneumonitis, thyroiditis, perineuritis and panniculitis developed. Manifestations including kidney disease (Table, lower) were cured by anti-DOCK8 Ab treatment.
We prove the self-organized criticality theory explaining that autoimmunity arises as a natural consequence of routine but exaggerated immune response against antigen when stimulated maximally beyond immune systemfs self-organized criticality and show that DOCK8+CD4 T cell causes SLE.
To cite this abstract in AMA style:Shiozawa S, Tsumiyama K, Miyazaki Y, Sakurai K, Miyazawa M. Dock8-Positive CD4 T Cell As Autoantibody-Inducing CD4 T (aiCD4 T) Cell That Causes Systemic Lupus Erythematosus (SLE): Proof of Concept of Self-Organized Criticality Theory As a Cause of SLE [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/dock8-positive-cd4-t-cell-as-autoantibody-inducing-cd4-t-aicd4-t-cell-that-causes-systemic-lupus-erythematosus-sle-proof-of-concept-of-self-organized-criticality-theory-as-a-cause-of-sle/. Accessed June 15, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/dock8-positive-cd4-t-cell-as-autoantibody-inducing-cd4-t-aicd4-t-cell-that-causes-systemic-lupus-erythematosus-sle-proof-of-concept-of-self-organized-criticality-theory-as-a-cause-of-sle/