*Purpose: We evaluated the immune reconstitution of recipients of HLA matched combined kidney and hematopoietic cell transplants after tolerance induction

*Methods: Twenty nine recipients of living donor kidney transplants were given enriched donor CD34+ hematopoietic cells and T cell following a conditioning regimen consisting of anti-thymocyte globulin (ATG) and low dose total lymphoid irradiation (TLI). Patients with mixed chimerism for at least 6 months were completely withdrawn from immunosuppressive (IS) drugs between months 6 to 17.

*Results: Twenty four patients were successfully withdrawn from IS drugs. Twenty-three showed no evidence of clinical or microscopic rejection with up to 8 years follow up. Ten of the 24 patients showed persistence of mixed chimerism of T cells, B cells, NK cells, and granulocytes for at least 2 years, and 14 lost chimerism during this period. Freedom of rejection off IS drugs was observed with or without loss of chimerism. No patients developed evidence of graft versus host disease (GVHD). Chimerism among T cells in the blood at all time points was significantly reduced as compared to all other lineages including B cells, NK cells, granulocytes, CD34 hematopoietic progenitors, and whole blood. Mean percent chimerism among B cells was about 30% higher than that of T cells. Although there was a similar profound depletion of blood naive T and B cells immediately after conditioning with TLI and ATG, there was a difference in the kinetics of immune reconstitution during the first year post-Tx. There was a marked increase in the percentage and absolute number of B cell precursors (CD19+CD20-CD38+IgD- pro-B cells) among all CD19+ B cells that peaked at about 6 weeks post-Tx in association with the marked reduction in the percentage of naive B cells(CD19+CD20+IgD+).However, by 6 months post-Tx, the percentage of naive B cells and pro-B cells returned pre-Tx levels. In contrast, the frequency of thymic T cell precursors in the blood, identified by TCR excision circle (TREC) analysis, was reduced to almost undetectable levels at 6 weeks post-Tx along with a marked reduction of (CD45RO-CD62L+) naive T cells. The reduction of T cells and T cell precursors began to gradually recover after 6 months, and did not approach the pre-Tx levels until the second year post-Tx.

*Conclusions: Persistence of mixed chimerism for a least 6 month was associated with successful withdrawal of IS drugs in a majority of recipients of combined HLA matched kidney and hematopoietic cell transplants receiving a TLI ATG conditioning regimen. We observed a marked delay in T cell reconstitution as compared to B cell reconstitution associated with low levels of chimerism among T cells as compared to B cells. The low levels of donor chimerism among T cells is likely to have contributed to the absence of GVHD.

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