CD69 downregulates autoimmune reactivity through active transforming growth factor-beta production in collagen-induced arthritis

J Clin Invest. 2003 Sep;112(6):872-82. doi: 10.1172/JCI19112.


CD69 is induced after activation of leukocytes at inflammatory sites, but its physiological role during inflammation remains unknown. We explored the role of CD69 in autoimmune reactivity by analyzing a model of collagen-induced arthritis (CIA) in WT and CD69-deficient mice. CD69-/- mice showed higher incidence and severity of CIA, with exacerbated T and B cell immune responses to type II collagen. Levels of TGF-beta1 and TGF-beta2, which act as protective agents in CIA, were reduced in CD69-/- mice inflammatory foci, correlating with the increase in the proinflammatory cytokines IL-1beta and RANTES. Local injection of blocking anti-TGF-beta antibodies increased CIA severity and proinflammatory cytokine mRNA levels in CD69+/+ but not in CD69-/- mice. Moreover, in vitro engagement of CD69 induced total and active TGF-beta1 production in Concanavalin A-activated splenocyte subsets, mouse and human synovial leukocytes, and Jurkat stable transfectants of human CD69 but not in the parental CD69 negative cell line. Our results show that CD69 is a negative modulator of autoimmune reactivity and inflammation through the synthesis of TGF-beta, a cytokine that in turn downregulates the production of various proinflammatory mediators.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antigens, CD / metabolism*
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • Antigens, Differentiation, T-Lymphocyte / metabolism*
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / metabolism*
  • Autoimmunity / physiology*
  • Cytokines / genetics
  • Cytokines / immunology
  • Cytokines / metabolism
  • Down-Regulation*
  • Foot / pathology
  • Humans
  • Inflammation / immunology
  • Joints / cytology
  • Joints / pathology
  • Lectins, C-Type
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Spleen / cytology
  • Spleen / pathology
  • Synovial Fluid / cytology
  • Synovial Fluid / immunology
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism*


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Cytokines
  • Lectins, C-Type
  • Transforming Growth Factor beta