LoCascio, Samuel A.Morokata, TatsuakiChittenden, MeredithPreffer, FredericDombkowski, David M.Andreola, GiovannaCrisalli, KerryKawai, TatsuoSaidman, SusanSpitzer, ThomasTolkoff-Rubin, NinaCosimi, A.Sachs, DavidSykes, Megan2016-07-112010LoCascio, Samuel A., Tatsuaki Morokata, Meredith Chittenden, Frederic I. Preffer, David M. Dombkowski, Giovanna Andreola, Kerry Crisalli, et al. 2010. “Mixed Chimerism, Lymphocyte Recovery, and Evidence for Early Donor-Specific Unresponsiveness in Patients Receiving Combined Kidney and Bone Marrow Transplantation to Induce Tolerance.” Transplantation 90, no. 12: 1607–1615. doi:10.1097/tp.0b013e3181ffbaff.0041-1337http://nrs.harvard.edu/urn-3:HUL.InstRepos:27526393Background We have previously reported operational tolerance in patients receiving HLA-mismatched combined kidney and bone marrow transplantation (CKBMT). We now report on transient multilineage hematopoietic chimerism and lymphocyte recovery in five patients receiving a modified CKBMT protocol, and evidence for early donor-specific unresponsiveness in one of these patients. Methods Five patients with end-stage renal disease received CKBMT from HLA-mismatched, haploidentical living related donors following modified non-myeloablative conditioning. Polychromatic flow cytometry (FCM) was used to assess multilineage chimerism where evaluable and lymphocyte recovery post-transplant. Limiting dilution analysis was used to assess helper-T-lymphocyte reactivity to donor antigens. Results Transient multilineage mixed chimerism was observed in all patients but chimerism became undetectable by 2 weeks post-CKBMT. A marked decrease in T and B lymphocyte counts immediately following transplant was followed by gradual recovery. Initially recovering T cells were depleted of CD45RA+/CD45RO− “naïve-like” cells, which have shown strong recovery in two patients and CD4/CD8 ratios increased immediately following transplant but then declined markedly. NK cells were enriched in the peripheral blood of all patients following transplant. For Subject 2, a pre-transplant limiting dilution assay revealed T helper cells recognizing both donor and third-party PBMCs. However, the anti-donor response was completely undetectable by Day 24, while third-party reactivity persisted. Conclusion These results characterize the transient multilineage mixed hematopoietic chimerism and recovery of lymphocyte subsets in patients receiving a modified CKBMT protocol. The observations are relevant to the mechanisms of donor-specific tolerance in this patient group.en-USBone marrow transplantationtoleranceimmunosuppressionkidneymixed chimerismJournal Article2016-07-1110.1097/TP.0b013e3181ffbaff