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Langerhans cell homeostasis and turnover after nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation.

Abstract：

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.

journal_name

Transplantation

journal_title

Transplantation

authors

Mielcarek M,Kirkorian AY,Hackman RC,Price J,Storer BE,Wood BL,Leboeuf M,Bogunovic M,Storb R,Inamoto Y,Flowers ME,Martin PJ,Collin M,Merad M

doi

10.1097/TP.0000000000000097

subject

Has Abstract

pub_date

2014-09-15 00:00:00

pages

563-8

issue

eissn

0041-1337

issn

1534-6080

journal_volume

pub_type

临床试验,杂志文章

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Langerhans cell homeostasis and turnover after nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation.