Identification of murine placental glycoproteins in relation to in vivo and in vitro immunomodulatory properties against H-2 antigens.
Glycoproteins were fractionated from placentae of syngeneic mice (CBA female xCBA male - H-2k) and evaluated in vivo and in vitro for the modulation of allo-immune responses against the H-2 incompatible A/J (H-2a) strain. It became apparent that the placenta contained high (309-800 kDA) and low (less than 13 kDA) molecular weight proteins, which favoured Sa1 allograft enhancement, leading to 75-100% lethal tumors, and inhibited mixed lymphocyte cultures (MLC). Though the low molecular weight fraction did not modify the mast cell degranulating (DAAD) antibody response, high molecular weight proteins caused a low production of DAAD allo-antibodies of the IgG1 + IgE isotypes. Moreover, addition of the placental fraction representing a specific band of 119 kDA resulted in the production of allo-immune sera rich in DAAD antibodies, which, however, were not associated with allograft enhancement. Beside these components, placenta is endowed with other proteins which modify humoral immune responses in different ways, as ascertained by the C-mediated cytotoxic antibody assay; fractions, rich in a 105 and 55 kDA bands, were immunosuppressive, whereas another, rich in a specific 100 kDA band, was active in eliciting enhanced production of alloantibodies of the IgG2 isotype. Moreover, the fractions representing specific bands of 50, 68 and 75 kDA, which were most effective in inhibiting MLC, neither caused lethal tumor enhancement nor modified IgG2 antibody responses. Based on in vivo and in vitro modulation of immune responses by placental products, it is concluded that: 1) allograft enhancement and high production of IgG1 antibodies are not linked to the same glycoprotein, 2) the immunomodulators in relation to the protection of viviparity appear to be located at the exclusion limits of Sephacryl S-200 (i.e. greater than 250 kDA and less than 13 kDA proteins) and 3) in vitro assays which depend on the inhibition of MLC by placental components should not be taken as the sole criterion for defining a given immunomodulator.
Gupta
G S
GS
INSERM U 23, Hôpital Saint-Antoine, Paris.
Kinsky
R G
RG
D000818:Animals; D003208:Concanavalin A; D003602:Cytotoxicity, Immunologic; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology*; D007108:Immune Tolerance; D007518:Isoantibodies / Q000096:biosynthesis; D007959:Lymphocyte Culture Test, Mixed; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008970:Molecular Weight; D010920:Placenta / Q000276:immunology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology*
D006023:Glycoproteins; D006183:H-2 Antigens; D007518:Isoantibodies; D003208:Concanavalin A