The Journal of Experimental Medicine
Keystone Symposia
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Published online 3 January 2006 doi:10.1084/jem.20051787
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 1, 27-33
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BRIEF DEFINITIVE REPORT

 The fate of human Langerhans cells in hematopoietic stem cell transplantation

Matthew P. Collin1, Derek N.J. Hart2, Graham H. Jackson1, Gordon Cook3, James Cavet4, Stephen Mackinnon5, Peter G. Middleton1, and Anne M. Dickinson1

1 Haematological Sciences, University of Newcastle, Newcastle upon Tyne NE2 4HH, England, UK
2 Mater Medical Research Institute, South Brisbane, Queensland 4101, Australia
3 Department of Haematology, St. James's University Hospital, Leeds LS9 7TF, England, UK
4 Department of Haematology, Christie Hospital NHS Trust, Manchester M20 4BX, England, UK
5 Department of Haematology, Royal Free and University College London Medical School, London NW3 2QG, England, UK

CORRESPONDENCE Matthew Collin: matthew.collin{at}ncl.ac.uk

Langerhans cells (LC) and other antigen-presenting cells are believed to be critical in initiating graft versus host responses that influence the outcome of allogeneic hematopoietic stem cell transplantation. However, their fate in humans is poorly understood. We have sought to define the effect of conditioning regimes and graft versus host disease (GVHD) on the survival of recipient LC and reconstitution of donor cells after transplant. Confocal microscopy of epidermal sheets shows that full intensity transplant (FIT) depletes LC more rapidly than reduced intensity transplant (RIT) at day 0, although the nadir is similar in both at 14–21 d. Recovery occurs rapidly within 40 d in the absence of acute GVHD, but is delayed beyond 100 d when GVHD is active. LC chimerism was determined in sex-mismatched transplants using a two-step Giemsa/fluorescence in situ hybridization assay on isolated cells. Acquisition of donor chimerism at 40 d is more rapid after FIT (97%) than RIT (36.5%), irrespective of blood myeloid engraftment. At 100 d, all transplants achieve at least 90% LC donor chimerism and over half achieve 100%. Complete donor chimerism is associated with prior acute cutaneous GVHD, suggesting a role for allogeneic T cells in promoting LC engraftment.


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