Purpose: This study was designed to introduce immunotherapy with adoptive transfer of donor-specific chimeric cells to support allograft acceptance in composite tissue allograft (CTA) transplants.
Methods: Ten primary chimeras were created by intraosseous transplantation of 70x10⁶ BM cells across MHC barrier between LBN(RT1ⁿ) and ACI(RT1^a) donors (n=5/each) to Lewis(RT1^l) recipients under 7 days of αβ-TCRmAb/CsA protocol. Secondary chimeras were created via adoptive transfer of MACS-sorted primary chimeric cells to naïve Lewis rat. The induction of chimerism and migratory potential of chimeric cells (for MHC-class I antigens) in peripheral blood, BM, and lymphoid organs of secondary chimeras were evaluated by flow cytometry and immunohistochemistry. To test therapeutic effect of adoptive transfer of chimeric cells, groin flaps of donor origin were transplanted to secondary chimeras.
Results: In primary chimeras 9.5-12.0% of donor-specific chimerism was induced. After MACS sorting 9.0 - 20.0x10⁶ RT1ⁿ and the RT1^a chimeric cells were achieved. At day 7, adoptive transfer of chimeric cells induced chimerism in secondary chimeras at 10.3-21.0% for the RT1ⁿ and 4.6-16.4% for the RT1^a antigens. Prolonged donor flap survival was achieved after adoptive transfer of chimeric cells without chronic immunosuppression up to 150 days in secondary LBN chimeras and up to120 days in secondary ACI chimeras. Donor-origin cells were found in the lymphoid organs of primary and secondary chimeras.
Conclusion: Adoptive transfer of chimeric cells holds therapeutic potential for skin allograft acceptance without chronic immunosuppression. This approach may serve as a new therapeutic modality for tolerance induction in CTAs by direct intraosseous delivery of chimeric cells.