Background
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.
Methods
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.
Results
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.
Conclusions
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.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to The Journal of Heart and Lung TransplantationAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Systemic chimerism in human female recipients of male livers.Lancet. 1992; 340: 876-877
- Persistence of donor lymphocytes in liver allograft recipients.Transplantation. 1993; 56: 1001-1007
- Allogeneic lymphocyte chimerism after clinical lung transplantation.Transpl Immunol. 1995; 3: 74-80
- Development, stability, and clinical correlations of allogeneic microchimerism after solid organ transplantation.Transplantation. 1996; 61: 40-45
- Peripheral microchimerism in long-term cadaveric-kidney allograft recipients.Lancet. 1994; 343: 1468-1469
- Frequency and clinical correlations of allogeneic microchimerism after heart, liver, and lung transplantation.Transplant Proc. 1997; 29: 1215-1217
- Peripheral tolerance mechanisms prevent the development of autoreactive T cells in chimeras grafted with two minor incompatible thymuses.Eur J Immunol. 1989; 19: 111-117
- Migration patterns of dendritic leukocytes.Transplantation. 1990; 49: 1-7
- Transplantation milestones.JAMA. 1995; 273: 876-879
- Pulmonary dendritic cells.Am J Respir Crit Care Med. 2005; 172: 530-551
- BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood.J Immunol. 2000; 165: 6037-6046
- Identification and characterization of human pulmonary dendritic cells.Am J Respir Cell Mol Biol. 2005; 32: 177-184
- Isolation of myeloid and plasmacytoid dendritic cells from human bronchoalveolar lavage fluid.Immunol Cell Biol. 2006; 84: 267-273
- Increased bronchoalveolar lavage fluid CD1c expressing dendritic cells in idiopathic pulmonary fibrosis.Respiration. 2009; 78: 446-452
- Differential dynamics of donor DC and non-DC peripheral blood mononuclear cell microchimerism in lung transplantation.Clin Immunol. 2009; 133: 179-183
- Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria.J Heart Lung Transplant. 2002; 21: 297-310
- Patterns of donor-type microchimerism after heart transplantation.Lancet. 1994; 343: 1469-1471
- Fine quantitation by competitive PCR of circulating donor cells in posttransplant chimeric recipients.Transplantation. 1994; 58: 964-965
- TLR9/TLR7-triggered downregulation of BDCA2 expression on human plasmacytoid dendritic cells from healthy individuals and lupus patients.Clin Immunol. 2008; 129: 40-48
- Chimerism and donor-specific nonreactivity 27 to 29 years after kidney allotransplantation.Transplantation. 1993; 55: 1272-1277
- Donor cell chimerism permitted by immunosuppressive drugs: a new view of organ transplantation.Immunol Today. 1993; 14: 326-332
- Identification of a radio-resistant and cycling dermal dendritic cell population in mice and men.J Exp Med. 2006; 203: 2627-2638
- Chimerism in organ transplantation: conflicting experiments and clinical observations.Transplantation. 2003; 75: 13S
- Microchimerism and rejection: a meta-analysis.Clin Transplant. 2000; 14: 345-350
- Organ-specific patterns of donor antigen-specific hyporeactivity and peripheral blood allogeneic microchimerism in lung, kidney, and liver transplant recipients.Transplantation. 1995; 60: 1546-1554
- Microchimerism and renal transplantation: doubt still persists.Transplant Proc. 2007; 39: 948
- Sequential measurement of peripheral blood allogeneic microchimerism levels and association with pulmonary function.Transplantation. 1996; 62: 1811-1818
- Peripheral blood allogeneic microchimerism in lung and cardiac allograft recipients.J Leukoc Biol. 1999; 66: 306-309
- Development of bronchiolitis obliterans syndrome despite blood chimerism in human lung transplant recipients.Transpl Int. 1999; 12: 439
Article info
Publication history
Published online: March 10, 2011
Identification
Copyright
© 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
