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The fate of human Langerhans cells in hematopoietic stem cell transplantation

Lookup NU author(s): Professor Matthew CollinORCiD, Professor Graham Jackson, Dr Jennifer Cavet, Dr Peter Middleton, Professor Anne Dickinson

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Abstract

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. JEM © The Rockefeller University Press.


Publication metadata

Author(s): Collin MP, Hart DNJ, Jackson GH, Cook G, Cavet J, Mackinnon S, Middleton PG, Dickinson AM

Publication type: Article

Publication status: Published

Journal: Journal of Experimental Medicine

Year: 2006

Volume: 203

Issue: 1

Pages: 27-33

ISSN (print): 0022-1007

ISSN (electronic): 1540-9538

Publisher: Rockefeller University Press

URL: http://dx.doi.org/10.1084/jem.20051787

DOI: 10.1084/jem.20051787

PubMed id: 16390938


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