We have established high levels of durable chimerism and immunosuppression-free graft survival without GVHD or engraftment syndrome in recipients of living donor facilitating cell/hematopoietic stem cell/kidney allografts. In the present study we have prospectively analyzed recovery of immune function and persistence of vaccination memory in subjects who exhibit high levels of chimerism. Chimerism testing was performed using molecular short tandem report (STR) technology (sensitivity +5%). Three of four subjects who had been vaccinated to hepatitis B and whose donors had not been vaccinated retained their immunity following transplantation. This observation therefore suggests persistence of recipient immunologic memory. All subjects tested retained memory for varicella and the majority did as well for measles (9/11), mumps (8/11) and rubella (5/10). A blood group disparity was present in 9 chimeric donor/recipient pairs. One chimeric subject converted to donor blood type, 3 exhibit mixed donor/host RBC chimerism, and 5 retained their own blood type. These findings therefore suggest that mixed donor/host hematopoietic stem cell chimerism is present. Taken together, these data demonstrate that the conditioning regimen is very reduced in intensity. Six chimeric subjects have been immunized with pneumococcal vaccine. All generated an immune response to vaccination, confirming immunocompetence to generate an antibody response to antigen. Notably, recovery of CD8⁺ and CD4⁺ central memory, naÏve, and effector memory T cells occurred within one year post-transplantation to levels that were not significantly different from pre-transplantation. In addition, CD31⁺/CD45RA⁺ CD8⁺ and CD4⁺ T cells representative of recent thymic emigrants (RTE) were present by 3 months, demonstrating de novo thymic production of T cells after transplantation. Taken together these data suggest that immunologic recovery is robust in these chimeric subjects.

Bozulic, L.: Employee, Regenerex, LLC. Badder, M.: Employee, Regenerex, LLC. Ildstad, S.: Other, Regenerex, LLC, CEO.

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