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Specific immunosuppression of human anti-murine antibody responses in hu-PBL-SCID mice
S Bitoh1, G M Lang, D Kierek-Jaszczuk
1Department of Immunology, University of Manitoba, Winnipeg, Canada.
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.
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.