Induction of long-term specific tolerance to allografts in rats by therapy with an anti-CD3-like monoclonal antibody

Transplantation
M R NicollsB M Hall

Abstract

Monoclonal antibodies to CD3 have been shown to activate T cells in vivo and in vitro but have also been shown to render T cells anergic in vitro. In this study G4.18, a mouse IgG3 mAb, was produced that appeared to recognize CD3 by its binding to all peripheral T cells, including a population not recognized by mAb to TCR-alpha/beta that was presumed to be TCR-gamma/delta cells. It precipitated molecules in the 24-26 kd region consistent with the CD3 complex as well as molecules approximately 45 and approximately 49 kd that corresponded to TCR alpha and beta chains and a 92-kd complex. Incubating T cells for 24 hr with saturating concentrations of G4.18 caused modulation of the TCR complex. In vitro, it activated T cells but only if prebound to plastic. In solution it inhibited MLC and CML, but not PHA or Con A activation. In vivo, G4.18 was not toxic even in high doses, and this was thought to be due to the inability of this mAb to activate T cells in vitro because the rat lacks Fc receptors for mouse IgG3. Therapy with G4.18 resulted in transient modulation of TCR/CD3 on T cells and depletion of these cells from blood. G4.18 had no depleting effects by lymph node or spleen cells but caused marked, transient thymic involution....Continue Reading

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