Induction and suppression of anti-antibodies to syngeneic T cell-binding antibodies in mice

Clin Exp Immunol. 1997 Jul;109(1):180-4. doi: 10.1046/j.1365-2249.1997.4321331.x.


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.

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / biosynthesis*
  • Antibodies, Anti-Idiotypic / immunology*
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / genetics*
  • Antibodies, Monoclonal / immunology*
  • Bone Marrow Transplantation / immunology
  • Flow Cytometry
  • Graft vs Host Disease / immunology
  • Immunization
  • Immunoglobulin Fc Fragments / immunology
  • Immunoglobulin G / immunology
  • Immunoglobulin M / immunology
  • Immunosuppression Therapy
  • Mice
  • Mice, Inbred C57BL / genetics
  • Mice, Inbred CBA / genetics
  • Skin Transplantation / immunology
  • Species Specificity
  • T-Lymphocytes / immunology*


  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal
  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • Immunoglobulin M