콜라겐 유도 관절염에서 콜라겐 항원 특이 $V{\beta}3$+CD4+T 세포의 선택적 증식

Selective Expansion of TCR $V{\beta}3$+CD4+T Cells in Collagen-induced Arthritis in DBA/1 Mice

  • 이재선 (가톨릭대학교 의과학연구원 류마티스연구센터) ;
  • 조미라 (가톨릭대학교 의과학연구원 류마티스연구센터) ;
  • 이정은 (가톨릭대학교 의과학연구원 류마티스연구센터) ;
  • 민소연 (가톨릭대학교 의과학연구원 류마티스연구센터) ;
  • 윤종현 (가톨릭대학교 의과학연구원 류마티스연구센터) ;
  • 김완욱 (가톨릭대학교 의과학연구원 류마티스연구센터) ;
  • 민준기 (가톨릭대학교 의과학연구원 류마티스연구센터) ;
  • 박성환 (가톨릭대학교 의과학연구원 류마티스연구센터) ;
  • 김호연 (가톨릭대학교 의과학연구원 류마티스연구센터)
  • Lee, Jae-Seon (Rheumatism Research Center, Catholic Institute of Medical Science, The Catholic University of Korea) ;
  • Cho, Mi-La (Rheumatism Research Center, Catholic Institute of Medical Science, The Catholic University of Korea) ;
  • Lee, Jung-Eun (Rheumatism Research Center, Catholic Institute of Medical Science, The Catholic University of Korea) ;
  • Min, So-Youn (Rheumatism Research Center, Catholic Institute of Medical Science, The Catholic University of Korea) ;
  • Yoon, Chong-Hyeon (Rheumatism Research Center, Catholic Institute of Medical Science, The Catholic University of Korea) ;
  • Kim, Wan-Uk (Rheumatism Research Center, Catholic Institute of Medical Science, The Catholic University of Korea) ;
  • Min, Jun-Ki (Rheumatism Research Center, Catholic Institute of Medical Science, The Catholic University of Korea) ;
  • Park, Sung-Hwan (Rheumatism Research Center, Catholic Institute of Medical Science, The Catholic University of Korea) ;
  • Kim, Ho-Youn (Rheumatism Research Center, Catholic Institute of Medical Science, The Catholic University of Korea)
  • 발행 : 2005.06.30

초록

Background: Collagen-induced arthritis (CIA) in mice is animal model of autoimmune disease known as rheumatic arthritis in human. We investigated CII-specific CD4+ T cell receptor usage in CIA mice. Methods: In CIA model, draining lymph node (dLN) CD4+ T cells and splenocytes at $3^{rd},\;5^{th},\;8^{th}$ week, we investigated CII-specific T cell proliferation, production of IL-17, IFN-${\gamma}$, TNF-${\alpha}$, IL-4 and IL-10. And we also performed anti-CII IgG Ab measurements in serum level, TCRV ${\beta}$ usage and T cell clonality with RT-PCR-SSCP analysis. Also, we performed proliferative response against CII when CII-specific T cell subset is deleted. Results: CIA mice showed more increase in the serum level of anti-CII IgG than normal mice after induction of arthritis. And the level of anti-CII IgG2a in CIA mice was increased after $3^{rd}$ week after primary immunization, while anti-CII IgG1 was decreased. Draining LN CD4+ T cells have proliferated against CII stimulation at $3^{rd}$ week after $1^{st}$immunization. CD4+T cells derived from dLN of CIA mice produced proinflammatory cytokine IFN-${\gamma}$, IL-17 etc. Draining LN CD4 T cells of CIA presented higher proportion of CD4+V ${\beta}3$+subset compared to those of normal mice at $3^{rd}$ week after $1^{st}$ immunization, and they were increased in proportion by CII stimulation. Draining LN CD4+ T cells without TCRV ${\beta}3+/V{\beta}8.1/8.2+/V{\beta}$10b+cells were not responsive against CII stimulation. But, CII-reactive response of TCRV ${\beta}3-/V{\beta}8.1/8.2-/V{\beta}$10b- T cells was recovered when $V{\beta}3+$ T cells were added in culture. Conclusion: Our results indicate that CD4+$V{\beta}3+$ T cells are selectively expanded in dLN of CIA mice, and their recovery upon CII re-stimulation in vitro, as well as the production Th1-type cytokines, may play pivotal role in CIA pathogenesis.

키워드

참고문헌

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