Soluble Fibrinogen-Like Protein 2/Fibroleukin Exhibits Immunosuppressive Properties: Suppressing T Cell Proliferation and Inhibiting Maturation of Bone Marrow-Derived Dendritic Cells

• Published in: The Journal of immunology (1950) Vol. 170; no. 8; pp. 4036 - 4044
• Main Authors: Chan, Camie W. Y, Kay, Lyndsey S, Khadaroo, Rachel G, Chan, Matthew W. C, Lakatoo, Sophia, Young, Kevin J, Zhang, Li, Gorczynski, Reginald M, Cattral, Mark, Rotstein, Ori, Levy, Gary A
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.04.2003
• Subjects: 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
• ISSN: 0022-1767; 1550-6606
• 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.