Specific immunosuppressive activity of epiglycanin, a mucin-like glycoprotein secreted by a murine mammary adenocarcinoma (TA3-HA).
Epiglycanin (Epi) is a mucin-like glycoprotein carrying multiple Thomsen Freidenreich (TF) and Tn determinants secreted by a murine mammary adenocarcinoma, TA3-Ha. As an attempt to further characterize immunoregulatory networks in the TA3-Ha animal model, we tested whether Epi causes active suppression of the cell-mediated immune response against TF determinants. In this study, we show that (a) s.c. injection of epiglycanin emulsified in either complete Freund's adjuvant or Ribi adjuvant containing trehalose dimycolate and monophosphoryl lipid A elicits a classical specific delayed-type hyperactivity response to TF haptens either naturally expressed on epiglycanin or as synthetic haptens conjugated to a protein carrier; (b) i.v. injection of as little as 500 ng of Epi induces specific immunosuppression to anti-Epi and anti-TF synthetic antigen delayed-type hyperactivity responses; (c) this immunosuppression can be abrogated by i.v. injection of cyclophosphamide prior to immunizations; (d) Epi-induced specific immunosuppression can be adoptively transferred by nylon wool-nonadherent cells 6 days following i.v. injection of Epi; (e) pretreatment of suppressor cell populations with anti-Thy-1, anti-L3T4, anti-Lyt-1, or anti-I-Jk but not anti-Lyt-2 monoclonal antibodies plus complement prior to adoptive transfer abolished immunosuppression; (f) i.v. injection of immunosuppressive amounts of Epi on Days 2 and 6 after transplantation of TA3-Ha cells increased the lethality of the tumor transplant. These results suggest that Epi-induced specific immunosuppression in the TA3-Ha animal model is mediated by Thy-1+, L3T4+, Lyt-1+2-, and I-Jk+ suppressor cells. The results are also consistent with the suggestion that this immunosuppression may enhance TA3-Ha tumor growth.
Fung
P Y
PY
Department of Immunology, University of Alberta, Edmonton, Canada.
Longenecker
B M
BM
D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D015295:Antigens, Tumor-Associated, Carbohydrate; D003520:Cyclophosphamide / Q000494:pharmacology; D004187:Disaccharides / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006968:Hypersensitivity, Delayed / Q000188:drug therapy / Q000276:immunology; D007165:Immunosuppression Therapy; D007167:Immunotherapy; D007275:Injections, Intravenous; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D009363:Neoplasm Proteins / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology
D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D004187:Disaccharides; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C016424:epiglycanin protein, mouse; C016467:Thomsen-Friedenreich antigen; D003520:Cyclophosphamide