Soluble fibrinogen-like protein 2/fibroleukin exhibits immunosuppressive properties: suppressing T cell proliferation and inhibiting maturation of bone marrow-derived dendritic cells

J Immunol. 2003 Apr 15;170(8):4036-44. doi: 10.4049/jimmunol.170.8.4036.


Fibrinogen-like protein 2 (fgl2)/fibroleukin is a member of the fibrinogen-related protein superfamily. In addition to its established role in triggering thrombosis, it is known to be secreted by T cells. The soluble fgl2 ((s)fgl2) protein generated in a baculovirus expression system bound to both T cells and bone marrow-derived dendritic cells (DC) in a specific manner. (s)fgl2 exhibited immunomodulatory properties capable of inhibiting T cell proliferation stimulated by alloantigens, anti-CD3/anti-CD28 mAbs, and Con A in a dose-dependent manner; however, it had no inhibitory effects on CTL activity. The time- and dose-dependent inhibitory effect of (s)fgl2 on alloreactive T cell proliferation could be neutralized by a mAb against mouse fgl2. Polarization toward a Th2 cytokine profile with decreased production of IL-2 and IFN-gamma and increased production of IL-4 and IL-10 was observed in (s)fgl2-treated allogeneic cultures. Exposure of immature DC to (s)fgl2 abrogated the expression of CD80(high) and MHC class II(high) molecules and markedly inhibited NF-kappaB nuclear translocation, thus inhibiting their maturation. (s)Fgl2-treated DC had an impaired ability to stimulate allogeneic T cell proliferation. Maximal inhibition of proliferation was observed when allogeneic T cells were cultured with (s)fgl2-treated DC and (s)fgl2 protein was added in the culture. These data provide the first evidence to demonstrate that (s)fgl2 exerts immunosuppressive effects on T cell proliferation and DC maturation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology
  • B7-1 Antigen / biosynthesis
  • Baculoviridae / genetics
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Female
  • Fibrinogen / biosynthesis
  • Fibrinogen / genetics
  • Fibrinogen / metabolism
  • Fibrinogen / physiology*
  • Genetic Vectors
  • Growth Inhibitors / biosynthesis
  • Growth Inhibitors / genetics
  • Growth Inhibitors / metabolism
  • Growth Inhibitors / physiology*
  • Histocompatibility Antigens Class II / biosynthesis
  • Lymphocyte Activation / immunology
  • Lymphocyte Culture Test, Mixed
  • Mice
  • Mice, Inbred A
  • Mice, Inbred BALB C
  • Protein Binding / immunology
  • Solubility
  • Suppressor Factors, Immunologic / biosynthesis
  • Suppressor Factors, Immunologic / genetics
  • Suppressor Factors, Immunologic / metabolism
  • Suppressor Factors, Immunologic / physiology*
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Thromboplastin / biosynthesis
  • Thromboplastin / genetics
  • Thromboplastin / metabolism
  • Thromboplastin / physiology*


  • B7-1 Antigen
  • Cytokines
  • Fgl2 protein, mouse
  • Growth Inhibitors
  • Histocompatibility Antigens Class II
  • Suppressor Factors, Immunologic
  • Fibrinogen
  • Thromboplastin