The effectiveness of pretreatment with soluble or membrane-bound donor class I major histocompatibility complex antigens in the induction of unresponsiveness to a subsequent rat renal allograft.

Abstract

We have examined the ability of two physical forms of RT1.A class I molecules to induce immunologic unresponsiveness to renal allografts in the rat. Both preparations of class I MHC antigen were derived from rat liver. Class I MHC antigen was presented either as purified membrane-bound molecules incorporated into protein micelles or as a water-soluble preparation containing soluble RT1.A class I molecules. The amount of RT1.A class I contained in each preparation was compared with the amount of class I antigen expressed by whole viable liver cells by quantitative absorption analysis using F16.4.4.11 mAb. The results demonstrated that DA recipients pretreated with a single dose of 1.75 x 10(10) cellular equivalents or multiple doses of 5 x 10(9) cellular equivalents of purified LEW membrane-bound class I molecules, delivered in aggregated micelle form, accepted their LEW renal allografts indefinitely (MST greater than 100 days). In contrast, no prolongation of graft survival was observed using the liver cell cytosol preparation containing soluble RT1.A class I molecules (MST 10 days) at the concentrations tested (10(8) -3 x 10(8) cell equivalents). However, when preoperative treatment with single (greater than or equal to 5 x 10(7) cellular equivalents of soluble class I MHC antigen) or multiple doses (greater than or equal to 10(7) cellular equivalents per dose) of the liver cell cytosol preparation was combined with a subtherapeutic dose of CsA given postoperatively (day +2, 10 mg/kg), suppression of renal allograft rejection was achieved with long-term survival (MST greater than 100 days). The immunologic unresponsiveness observed in both cases was donor specific.