Schistosome-Derived Inhibitory Factor: An Immunosuppressive Agent Preferentially Active on T Lymphocytes

Abstract

We have previously shown that schistosome-derived inhibitory factors (SDIF) inhibited lymphocyte proliferation and induced immunosuppression. Crude SDIF was purified by successive gel filtration and reverse-phase high-performance liquid chromatography. Purified SDIF preparations strongly inhibited the proliferation of different T cell line cells, while other cell lines (B cells, macrophages and fibroblasts) were almost not affected by SDIF. The inhibition of T cell proliferation by SDIF was not mediated through an Interleukin-2-dependent mechanism since both Interleukin-2-dependent and -independent T cells were inhibited. SDIF-activity was absorbed by cells in a time- and cell-number-dependent fashion at 4°C, suggesting the existence of a possible receptor for SDIF. However, the difference in sensitivity to SDIF proliferation inhibition could not be attributed to the presence or absence of this receptor since cells from SDIF-sensitive and SDIF-resistant cell lines absorbed SDIF activity in the same way.

Effect of Schistosome-Derived Inhibitory Factor on the Cell Cycle of T Lymphocytes

“…This inhibitory effect was not merely due to the inhi bition of 3H-TdR uptake but to a real effect on cell proliferation because the number of cells was effec tively reduced in SDIF treated cultures and the same inhibitory effect was also observed when prolifera tion of T cell line cells was assayed by an enzymatic method [6].…”

“…The detailed purification procedure has been previously de scribed [6], In order to get a high amount of purified material, a semi-preparative reverse-phase column CB (Lichroprep RP-8, 310x25 mm, Merck, Darmstadt, FRG) equilibrated in water was used for HPLC. 200 mg of crude material was loaded and elution was performed with a linear gradient from 0 to 50% acetonitrile at a How rate of 5 ml/min.…”

“…In vivo injection of SDIF simultaneously with antigen decreased the specific IgE and IgG antibody production [4], In vitro, SDIF inhibited the generation of cytotoxic T lymphocytes in mixed lymphocyte cultures as well as the genera tion of suppressive T cells [5], Recently, using purified SDIF preparations, we were able to show that SDIF inhibited preferentially T cell proliferation and has almost no effect on the proliferation of B, macro phage and other cell lines [6]. The inhibition of T cell proliferation was not mediated at the level of an in terleukin 2 (IL-2)-dependent mechanism since both IL-2-dependent and -independent T cell lines were in hibited by SD IF [6].…”

Cytogenetic Studies on Blood Lymphocytes From Patients With Schistosoma Mansoni

“…mansoni infection have indicated the existance of parasite toxins circulating in the blood that affect the host immunity (22). Immunosuppressive agent which purified from the schistosomula of S. mansoni was found to act preferentially on Tlymphocytes, inhibiting their proliferation (23). Thus these observations may explain the cause of reduction in the levels of MI and RI (Table II).…”

On the Mechanisms of the Protective Effect of Infections on Type 1 Diabetes

“…Other mechanisms could be proposed as suggested by recent data obtained for the hepatitis A virus (which stimulates Th2 cells expressing the HAV receptor) (McIntire et al, 2001) and immunosuppression by a measles virus protein (Marie et al, 2001) and by various parasites (Mazingue et al, 1986).…”