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Abstract Number: 109

Targeting CD6 Expression Attenuates T Cell Activity in Murine Collagen Induced Arthritis

Yan Li 1, Jeffrey H. Ruth 2, Stephanie Rasmussen 3, Kalana S. Athukorala 2, Daniel P. Weber 2, M. Asif Amin 2, Phillip Campbell 3, Nora Singer 4, David Fox5 and Feng Lin 1, 1Cleveland Clinic, Cleveland, OH, 2University of Michigan, Ann Arbor, MI, 3Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 4The MetroHealth System -Case Western Reserve University School of Medicine, Cleveland, OH, 5Division of Rheumatology, Department of Internal Medicine, Autoimmunity Center of Excellence,University of Michigan, Ann Arbor, MI

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: Animal models, Antibodies, cytokines and chemokines, T cells

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Session Information

Date: Sunday, November 10, 2019

Session Title: T Cell Biology & Targets in Autoimmune & Inflammatory Disease Poster

Session Type: Poster Session (Sunday)

Session Time: 9:00AM-11:00AM

Background/Purpose: CD6, an important regulator of T cell function, interacts with the ligands CD166 and CD318. We previously examined CD318 expression on synovial tissues (STs) and soluble CD318 concentrations in synovial fluids (SFs) of rheumatoid arthritis (RA) patients and demonstrated its potential roles in recruitment and retention of T cells in the RA joints. To further clarify the significance of CD6 in RA, we examined the effects of targeting CD6 in the mouse collagen-induced arthritis (CIA) model, using CD6 knockout mice and CD6 humanized mice that express human CD6 in lieu of mouse CD6 on their T cells.

Methods: We immunized age- and sex-matched WT and CD6 KO mice with a collagen emulsion to induce CIA. Beginning on day 21, CIA clinical scores were recorded by a blinded investigator until day 28. For treatment studies using humanized CD6 mice, we immunized similarly, and injected UMCD6 (a mouse anti-human CD6 IgG) or control IgG on days 7, 14, and 21. We analyzed the joints of the paws for tissue damage, leukocyte infiltration, and local inflammatory cytokine production. We also compared collagen-specific Th1, Th9 and Th17 responses and serum levels of collagen-specific IgG subclasses. Cytokine multiplex assays were used to measure the levels of 32 inflammatory cytokines in homogenates of paw and joint tissues.

Results: CD6 KO mice had markedly lower clinical arthritis scores than WT mice (p< 0.05) suggesting that CD6 acts to tune the severity of joint inflammation in CIA. Absence of CD6 reduced 1) collagen-specific Th9 and Th17, but not Th1 responses, 2) many pro-inflammatory joint cytokines, 3) serum levels of collagen-reactive IgG1 and IgG2b, but not IgG2a and IgG3. Significant reductions in joint homogenate hemoglobin (Hb) content in CD6 KO mice were observed compared to WT mice (reduced angiogenesis). Moreover, treating CD6 humanized mice with a mouse anti-human CD6 monoclonal antibody was similarly effective in reducing joint inflammation in CIA as in reducing inflammatory cytokines and chemokines without significantly depleting T cells.

Conclusion: Taken together, these data suggest that CD6 is required for the development of CIA, and that CD6 could be targeted for treating RA.


Disclosure: Y. Li, None; J. Ruth, None; S. Rasmussen, None; K. Athukorala, None; D. Weber, None; M. Amin, None; P. Campbell, None; N. Singer, None; D. Fox, None; F. Lin, None.

To cite this abstract in AMA style:

Li Y, Ruth J, Rasmussen S, Athukorala K, Weber D, Amin M, Campbell P, Singer N, Fox D, Lin F. Targeting CD6 Expression Attenuates T Cell Activity in Murine Collagen Induced Arthritis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/targeting-cd6-expression-attenuates-t-cell-activity-in-murine-collagen-induced-arthritis/. Accessed January 20, 2021.
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