Injection of donor-derived splenic dendritic cells plus a nondepleting anti-CD4 monoclonal antibody to prolong primary skin graft survival indefinitely and abrogate the production of donor-specific antibodies in the Fischer-to-Lewis rat combination.

ABSTRACT

We have previously shown that injection of donor-derived Fischer rat OX62+ dendritic cells plus an anti-CD4 monoclonal antibody generates donor-specific CD4+CD25+FoxP3+ regulatory T cells in Lewis rats spleens. The regulatory T cells indefinitely prolonged the survival of skin graft from Fischer rat and abrogated the antidonor antibody response. We have now shown that an injection of 2 × 10(6) donor-derived OX62+ dendritic cells plus 2 mg nondepleting anti-CD4 monoclonal antibody (W3/25) at 28 days before grafting induced indefinite skin graft survival in this combination; whereas an injection on day -1 prolonged it only to 50 days. This effect is donor specific. In both cases, we suppressed the antidonor antibody response. It is likely that the efficacy of this protocol is, at least in part, dependent on induction of donor-specific regulatory T cells, as suggested by previous data. The 28 days necessary to obtain tolerance of allogenic skin grafts may be due to the time required for the host to induce proliferation of donor-specific regulatory T cells.