have T cells that are hyperproliferative. sFGL2 is capable of inhibiting the proliferation of T cells stimulated by alloantigens and this inhibition is alleviated by the addition of a monoclonal antibody against sFGL2’s fibrinogen-like domain (FRED).12 When the supernatants of these T cell cultures are analyzed, they showed a predominant Th2 type polarization with upregulated levels of expression of interleukin-4 (IL-4) and Interleukin-10 (IL-10).12 There are also downregulated levels of Th1-type cytokines such as interleukin-2 (IL-2) and interferon γ (IFN-γ). This shows that sFGL2 largely inhibits the Th1 type response needed to activate cytotoxic lymphocytes to clear HCV infections. Additionally, sFGL2 can inhibit the maturation of immature dendritic cells (DCs) by preventing NF-κB translocation to the nucleus and subsequent expression of the co-stimulatory molecule CD80 and major histocompatibility complex II (MHC II). Therefore, sFGL2 may contribute to the negative regulatory activity exhibited by Treg cells. sFGL2 works to repress immune response through its FRED Domain. The immunosuppressive activity of sFGL2 has been localized to the C-terminal region containing the FRED domain. sFGL2’s FRED domain shares significant homology to the fibrinogen related domains of potent immunoregulatory molecules like cytotaxin and tenascin.12 This works to repress immune responses by binding to the inhibitory FC receptor, FCγRIIB. Furthermore, HCV’s core protein has been found to increase the levels of expression of sFGL2 and cause virus-specific CD4+ T lymphocytes to skew largely toward a Th2 lineage, allowing for the establishment of a chronic infection.13 Clinical significance Human Fibrinogen-like protein 2 may be useful as a biomarker for responsiveness to antiviral therapy. References [12] Chan CW et al. "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. Further reading