The mixed epidermal cell-lymphocyte reaction. II. Epidermal Langerhans cells are responsible for the enhanced allogeneic lymphocyte-stimulating capacity of normal human epidermal cell suspensions.

Earlier studies carried out in our laboratory which demonstrated that disaggregated human epidermal cells isolated from normal flexor forearm skin produced a greater degree of primary allogeneic lymphocyte blastogenic response than did autologous peripheral blood mononuclear cells have since been confirmed by others. We have now completed a series of additional studies designed to determine the basis for this difference. Blocking studies with anti-HLA-DR antibodies revealed that the allogeneic response triggered by epidermal cells was completely dependent on the presence of unbound HLA-DR molecules eliminating the possibility that nonspecific mitogenic effects produced by the epidermal cell suspension might be responsible for the difference. In addition we were unable to demonstrate that epidermal keratinocytes were supplying a nonspecific helper or growth-promoting effect to the interaction between stimulating HLA-DR bearing Langerhans cells and responding T lymphocytes. Since it has recently been suggested that the entire alloantigen-presenting capacity of unfractionated peripheral blood mononuclear cells can be attributed to a small population of HLA-DR antigen-bearing dendritic cells, we have considered the possibility that the greater degree of allogeneic lymphocyte response produced by epidermal cells could be due to the presence of a greater percentage of HLA-DR positive dendritic cells present in epidermal cell suspensions (i.e., Langerhans cells). Peripheral blood dendritic cell-enriched fractions and epidermal cell suspensions that contained similar percentages of dendritic cells produced equivalent amounts of allogeneic lymphocyte stimulation, whereas peripheral blood dendritic cell-enriched fractions that contained greater percentages of dendritic cells than were present in epidermal cell suspensions produced greater amounts of allogeneic stimulation. We therefore conclude that the enhanced mixed lymphocyte reaction stimulating capacity of human epidermal cell suspensions could be explained by the fact that epidermal cell suspensions contain a greater percentage of HLA-DR bearing alloantigen-presenting dendritic cells than do unfractionated peripheral blood mononuclear cell suspensions.