Nondepleting anti-CD4 monoclonal antibody enhances the ability of oral alloantigen delivery to induce indefinite survival of cardiac allografts: Oraltolerance to alloantigen

Background. We examined whether oral administration of alloantigen could in duce the prolonged survival of cardiac allografts. Methods. Hearts from CBK (H2(k)+K-b) transgenic or (C57BL/10xCBA)F1 (H2(b)x H2(k)) mice were transplanted into CBA(H2(k)) recipients pretreated orally with 1x10(7) donor splenocytes in the presence or absence of a nondepleting anti-CD4 (YTS 177, 200 mug/dose). Results. Modest prolongation of CBK cardiac grafts was induced in CEA mice fed with multiple doses of CBK splenocytes (MST 42 days compared with contr ols fed with syngeneic CBA splenocytes, 12 days). When the CD4 monoclonal a ntibody, YTS177, was administered for 2 days before the first oral delivery of CBR splenocytes, all mice accepted their grafts indefinitely (MST > 100 days versus mice treated with anti-CD4 alone, 11.5 days). To determine if feeding multiple doses of alloantigen was essential, CBA mice were given CB K splenocytes orally on a single occasion in combination with the anti-CD4, The majority of the grafts survived indefinitely (MST > 100 days). This or al treatment regimen also induced indefinite prolongation of (C57BL/10xCBA) F1 cardiac grafts. Conclusion. The induction of unresponsiveness by oral administration of all oantigen can be augmented by a nondepleting anti-CD4, YTS177, when given be fore the first oral delivery of allogeneic cells.