Langerhans cell homeostasis and turnover after nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation.
BACKGROUND
Langerhans cells (LCs) are self-renewing epidermal myeloid cells that can migrate and mature into dendritic cells. Recipient LCs that survive cytotoxic therapy given in preparation for allogeneic hematopoietic cell transplantation may prime donor T cells to mediate cutaneous graft-versus-host disease (GVHD). This possible association, however, has not been investigated in the setting of nonmyeloablative allografting.


METHODS
We prospectively studied the kinetics of LC-chimerism after sex-mismatched allogeneic hematopoietic cell transplantation with nonmyeloablative (n=23) or myeloablative (n=25) conditioning. Combined XY-FISH and Langerin-staining was used to assess donor LC-chimerism in skin biopsies obtained on days 28, 56, and 84 after transplant. The degree of donor LC-chimerism was correlated with the development of skin GVHD.


RESULTS
We observed significantly delayed donor LC-engraftment after nonmyeloablative transplantation compared with other hematopoietic compartments and compared with LC-engraftment after myeloablative conditioning. In most recipients of nonmyeloablative transplants, recipient LCs proliferated in situ, recruitment of donor-LCs was delayed by two months, and full donor LC-chimerism was only reached by day 84 after transplant. Although persistence of host LCs on day-28 after transplant was not predictive for acute or chronic skin GVHD, the recruitment of donor-derived LCs was associated with nonspecific inflammatory infiltrates (P=0.009).


CONCLUSIONS
These results show that LCs can self-renew locally but are replaced by circulating precursors even after minimally toxic nonmyeloablative transplant conditioning. Cutaneous inflammation accompanies donor LC-engraftment, but differences in LC conversion-kinetics do not predict clinical or histopathological GVHD.
1 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA. 2 University of Washington, Seattle, WA. 3 Immunology Institute, Mount Sinai Medical Center, New York, NY. 4 Tisch Cancer Institute, Mount Sinai Medical Center, New York, NY. 5 Institute of Cellular Medicine, Newcastle University, UK. 6 Address correspondence to: Marco Mielcarek, M.D., Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Mail Stop D1-100, PO Box 19024, Seattle, WA 98109.
Marco
M
Mielcarek
Anna Yasmine
AY
Kirkorian
Robert C
RC
Hackman
Jeremy
J
Price
Barry E
BE
Storer
Brent L
BL
Wood
Marylene
M
Leboeuf
Milena
M
Bogunovic
Rainer
R
Storb
Yoshihiro
Y
Inamoto
Mary E
ME
Flowers
Paul J
PJ
Martin
Matthew
M
Collin
Miriam
M
Merad
D000328:Adult; D000368:Aged; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology* / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006706:Homeostasis; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007801:Langerhans Cells / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000379:methods