An investigation into the mechanisms by which human dermis does not significantly contribute to the rejection of allo-skin grafts

The dermis is an important element in skin substitutes and in allo- or xeno-skin grafts. However, the reason(s) why dermis does not significantly induce the immune rejection reaction in vivo remain(s) hitherto unknown. To clarify the mechanisms underlying this phenomenon, we undertook the evaluation of: (i) the response of the peripheral blood mononuclear cells (PBM) to isolated allo-dermal cells or to pieces of or to whole allo-dermis, (ii) the migration and homing of the PBM inside allo-dermis or split thickness allo-skin, (iii) the distribution of the ICAM-1 protein within skin, and (iv) the features expressed by the PBM that migrate into allo-skin. The results herein presented show that (1) the isolated allo-dermal cells had the highest and the whole allo-dermis the lowest capacity to initiate the reactive proliferation of the PBM in vitro; (2) in an allo-skin/PBM co-culture model, most of the PBM slowly, yet preferentially, migrated to and homed inside the allo-epidermal compartment, instead of staying in the allo-dermis; (3) under the conditions employed, rather little ICAM-1 could be immunohistochemically detected within the epidermis, conversely, both the dermal cells and the dermal matrix were ICAM-1 positive; and (4) most of the PBM migrating into the allo-skin pieces expressed either the CD18 or the CD19 or the CD8 molecule, yet very few of them exhibited the LFA-1-antigen, and none of them were found to be CD4 positive. Therefore, we conclude that because the migrated PBM were LFA-1 negative, the ICAM-1-positive allo-dermal cells and matrix could not trap the migrating PBM by means of an ICAM-1/LFA-1 mechanism, and, therefore, the immunocompetent allo-dermal cells had no opportunity to get in touch and hence to stimulate the PBM. On the other hand, the PBM migrating into allo-skin, which exhibited either a CD18-positive or a CD19-positive or a CD8-positive phenotype, may constitute a very important subgroup of the whole PBM population specifically involved in the initiation of the immune rejection of skin allografts. Finally, we wish to point out that the PMB/skin co-culture model presently employed constitutes a useful tool for investigations into the migrating and homing patterns of lymphocytes.