Specific immunosuppression of human anti-murine antibody responses in hu-PBL-SCID mice.
Severe combined immunodeficient (SCID) mice were reconstituted with normal human peripheral blood leukocytes (PBLs) and were shown to produce a human anti-mouse immunoglobulin antibody response on immunization with heat-treated murine monoclonal IgG1 antibody to ovalbumin, referred to as ha-Mab-2. The human anti-mouse antibody response was proportional tot the number of B cells and mononuclear cells transferred from a given batch of PBL. However, pretreatment of hu-PBL-SCID mice with a tolerogenic covalent conjugate of monomethoxypolyethylene glycol (mPEG) and Mab-2 suppressed this response on subsequent injections of ha-Mab-2, and this suppression was shown to be antigen-specific, i.e., it did not suppress the antibody response to ovalbumin and did not affect the level of production of human immunoglobulin of hu-PBL-SCID mice. The suppression was due to the generation of human suppressor CD8+ T (Ts) cells, which down regulated CD4+ helper T cells in an antigen and HLA class I specific manner, i.e., these findings were in accord with the previously shown immunosuppressive effect of tolerogenic mPEG conjugates in normal mice.
Bitoh
S
S
Department of Immunology, University of Manitoba, Winnipeg, Canada.
Lang
G M
GM
Kierek-Jaszczuk
D
D
Fujimoto
S
S
Sehon
A H
AH
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D016827:CD8 Antigens / Q000032:analysis; D006801:Humans; D007108:Immune Tolerance; D007114:Immunization; D007136:Immunoglobulins / Q000097:blood; D017708:Leukocyte Transfusion; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D011092:Polyethylene Glycols; D050378:T-Lymphocytes, Regulatory / Q000502:physiology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D016827:CD8 Antigens; D007136:Immunoglobulins; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol