The tolerogenic molecule CD95-L is expressed on the plasma membrane of human activated, but not resting, Langerhans' cells.
Although dendritic cells (DC) are well known for their immunogenic capacities, they may even induce peripheral T-cell tolerance, and such a tolerogenic potential can be exerted in mouse through the expression on the DC plasma membrane of the CD95-ligand (CD95-L) molecule, which is able to trigger apoptosis of CD95-expressing antigen-specific T cells. We therefore asked whether epidermal DC, namely Langerhans' cells (LC), either resting (i.e. within the epidermis, 'in situ') or activated (i.e. suspended from the epidermis) or both, could express the CD95-L molecule on the plasma membrane. For such a purpose, two colloidal gold-immunoelectron microscopy (IEM) double-step procedures were carried out: an 'in situ' method, able to investigate resting LC, was performed on ultrathin frozen sections obtained by ultracryomicrotomy (UCMT) of normal skin biopsies; a pre-embedding (P-E) method, able to investigate suspended LC, was performed on epidermal cells (EC) suspended from normal skin specimens. In UCMT/IEM sections, resting LC showed gold particles within the cytoplasm but very rarely within organelles and never along the plasma membrane: resting LC are therefore capable of synthesizing CD95-L but not of expressing it in a functional location, thus autoreactive phenomena against CD95-expressing EC being avoided in normal epidermis. On the other hand, in P-E/IEM preparations, suspended LC showed several gold particles along the plasma membrane: activated LC are therefore capable of expressing CD95-L in a functional location, thus bearing the potential to exert tolerogenic capabilities against CD95-expressing T cells, e.g. to prevent inflammatory/autoimmune cutaneous disorders and/or favor the resolution thereof.
De Panfilis
G
G
Section of Dermatology, Department of Surgery, Parma University, Parma, Italy.
Venturini
M
M
Lavazza
A
A
Mommaas
M A
MA
Semenza
D
D
Torresani
C
C
Pasolini
G
G
D000911:Antibodies, Monoclonal; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D053222:Fas Ligand Protein; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism* / Q000648:ultrastructure; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism*; D016253:Microscopy, Immunoelectron
D000911:Antibodies, Monoclonal; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins