Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Mucosal Associated Invariant T Cells Contribute to the Pathogenesis of Arthritis.
Chiba, Asako, Tajima, Ryohsuke, Miyazaki, Yusei, Yamamura, Takashi, Miyake, Sachiko
MR1-restricted mucosal associated invariant T (MAIT) cells are a subset of innate lymphocytes which express an invariant TCRa chain (Va 19-Ja 33 in mouse and Va 7.2-Ja 33 in human) with a limited set of TCRb chains. We previously reported the regulatory role of MAIT cells in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. To understand their role in animal models of arthritis, we generated MR1-/- DBA1/J mice and analyzed their disease susceptibility to collagen-induced arthritis(CIA). We also investigated if MAIT cells are involved in the effector phase of arthritis by using two animal models of antibody-induced arthritis (AIA). Finally we studied mechanisms by which MAIT cells modulate autoimmune responses.
To obtain MR1-/- DBA1/J mice, MR1-/-C57BL/6 mice were backcroosed to DBA1/J mice for ten generations. To induce CIA, MR1-/- DBA/1J mice or WT littermates were immunized intradermally with bovine type II collagen (CII) (150mg) in Freund's complete adjuvant containing 250mg of H37Ra Mycobacterium tuberculosis on day 0 and CII in IFA on day 21. AIA was induced in MR1-/- C57BL/6 mice and WT littermates by injecting either K/BxN serum i.p. or a mixture of anti-type II collagen antibodies i.v. followed by lipopolysaccharide i.p. Va 19i T cells (mouse MAIT cells) were sorted from liver or spleen cells of Va19iTCR-Transgenic (Va 19iTg) CD1d-/- mice by using anti-TCRb and anti-NK1.1 monoclonal antibodies. In adoptive transfer studies, NK1.1+ TCRb+ Va19i T cells sorted from Va19iTg CD1d-/- mice were injected i.v. into MR1-/- mice on one day before the induction of arthritis. Cytokine producing capacity of MAIT cells stimulated with or without anti-CD3mAb in the presence of various types of cytokines was evaluated by ELISA or cytokine bead assay kit.
MR1-/- DBA/1J mice were more resistant to CIA compared to WT littermates, as demonstrated by clinical and histological scores of arthritis. CII specific antibody levels in the serum were reduced in MR1-/-DBA/1J mice compared to WT controls. The severity of clinical and pathological features of AIA was reduced in MR1-/- mice compared to control WT mice. MR1-/- mice reconstituted with MAIT cells developed severe forms of arthritis to the similar level of arthritis in WT mice. IL-17 production by anti-CD3mAb-stimulated MAIT cells was highly augmented in the presence of IL-23. In addition, MAIT cells were activated and produced IL-17 upon IL-23 stimulation even without TCR stimulation.
MAIT cells contribute to the pathogenesis of arthritis. MAIT cells may be activated by cytokines which are abundant in inflammatory arthritis, and this may in turn amplify autoimmune responses.
To cite this abstract, please use the following information:
Chiba, Asako, Tajima, Ryohsuke, Miyazaki, Yusei, Yamamura, Takashi, Miyake, Sachiko; Mucosal Associated Invariant T Cells Contribute to the Pathogenesis of Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2232