Induction and suppression of anti-antibodies to syngeneic T cell-binding antibodies in mice.
Considerable effort is being invested in antibody gene technologies for production of species-adapted anti-T cell antibodies which can overcome formation of neutralizing anti-antibodies (anti-Ab). By establishing a mouse model for the generation of syngeneic anti-T cell MoAb, we addressed the question of whether ideally species-adapted T cell-binding antibodies can prime mice to produce anti-Ab. Two anti-Thy-1.2 MoAbs of IgG2a (MmTC) or IgM (MmTC-IgM) isotype were generated in congenic C57B1/6-Thy-1.1 mice. Three injections of MmTC in C57B1/6-Thy-1.2 or (C57B1/6-Thy-1.2xC57B1/6-Thy-1.1)F1 hybrids where they act as syngeneic anti-T cell MoAbs induced low anti-Ab. When MmTC was injected as Igh-mismatched antibody in CBA/J mice, high titre anti-MmTC antibodies were measured and fully mismatched skin allografts rejected within 26 days. MmTC injected twice weekly in syngeneic C57B1/6 mice induced low anti-MmTC and prolonged graft survival up to day 117. In contrast, retreatment induced anti-MmTC with graft rejection within 32 days. Thus, upon retreatment, the immunosuppressive effects of MmTC were inhibited to a similar extent as that seen after antibody treatment in Igh-mismatched mice. However, a recently analysed immunological principle to suppress anti-Ab against T cell binding allo- or xenoantibodies by preinjection of T cell-depleting antibody with species differences in heavy chains also suppressed syngeneic anti-Ab after MmTC retreatment. This effect was accompanied by prolonged graft survival. Thus, our data indicate that inhibitory anti-Ab must be considered in humans even when treated with fully species-adapted anti-T cell MoAb, but may be suppressed by preinjection of a Fc region-mismatched anti-T cell antibody.
Kremmer
E
E
GSF-National Research Centre for Environment and Health, Institute for Immunology, München, Germany.
Mysliwietz
J
J
Thierfelder
S
S
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis* / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000276:immunology; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology; D007114:Immunization; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007165:Immunosuppression Therapy; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D008808:Mice, Inbred CBA / Q000235:genetics; D016038:Skin Transplantation / Q000276:immunology; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007075:Immunoglobulin M