Chimerism of dendritic cell subsets in peripheral blood after lung transplantation

Abstract

Passenger leukocytes of donor origin are transferred to the patient resulting in circulatory microchimerism after lung transplantation (LTx). This chimeric state has been shown to occur in the total leukocyte fraction as well as unseparated peripheral blood mononuclear cells (PBMCs). In this study we determined the microchimerism levels of B cells, monocytes, natural killer (NK) and T cells and dendritic cell (DC) subsets (mDC1, mDC2 and pDC) during the first year after lung transplantation. To identify circulating donor cells, 11 donor-patient combinations were selected, which were mismatched for HLA-B8. Analysis consisted of flow cytometry on a minimum of 1 million PBMCs taken monthly up to 1 year after LTx. Levels of microchimerism were found to be stable after LTx for all cell types investigated, although for NK+T cells an above-baseline chimerism of donor cells from the donor lung was observed in the first month after transplantation. Circulating PBMCs consisted of, on average, 0.002%, 1.7%, 0.03% and 0.001% of B cells, monocytes, NK+T cells and DCs, respectively, indicating that overall levels of microchimerism differed between the cell types investigated. In 2 patients no B-cell chimerism and in 1 patient no DC chimerism could be detected. Cell types and DC subsets of recipient origin were normally distributed. Conversely, monocytes, B cells and DCs of donor origin were increased and donor NK+T cells were decreased in number, compared with the recipient ratios. Analysis of circulating recipient DCs showed a normal distribution of mDC1s (70%), mDC2s (5%) and pDCs (25%). However, circulating donor DCs consisted of 80%, 20% and <1% of DC subsets mDC1, MDC2 and pDC, indicating that donor plasmacytoid dendritic cells were not detectable in the circulation. In the first year after lung transplantation a stable microchimerism was detected for all cell types investigated. However, donor pDCs were consistently absent in all samples investigated, which may be linked with graft rejection often observed after LTx.