Reconstitution of cutaneous neural immunological networks following bone marrow transplantation

During allogeneic bone marrow transplantation (BMT), host epidermal Langerhans cells (LC) are depleted and replaced by LC derived from the bone mar row inoculum. LC have recently been shown to form intimate spatial associations with intraepithelial nerves (IEN), which release regulatory peptides. The present study investigated whether the IEN network within skin remains intact during BMT, and whether repopulating LC re-establish contacts with IEN. Double-labeling immunohistochemical techniques were employed using antibodies to CD1a and neural cell adhesion molecule (CD56) to identify LC and IEN, respectively. LC were depleted by conditioning for BMT, and repopulating LC reached normal values after day +100. In contrast to fluctuations in the LC network, the frequency of LIEN remained unchanged during the post-BMT period. Contacts between LC and IEN were present both before and after BMT, and repopulating LC established a spatial interaction with IEN similar to that seen before BMT. These data provide the first evidence for the dynamic nature of the spatial relationship of LC with IEN, and raise intriguing questions regarding the mechanisms that direct homing of LC within epithelia.