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.