Effects of the immunosuppressive dipeptide L-leucyl-L-leucine O-methyl ester on epidermal Langerhans cells.
Pretreatment of newborn human foreskin epidermal cells (EC) with L-leucyl-L-leucine methyl ester (Leu-Leu-OME) was found to dramatically inhibit their ability to serve as alloantigen-presenting cells in a primary, one-way, allogeneic mixed epidermal cell-lymphocyte reaction (MECLR) without significantly affecting EC viability. The Leu-Leu-OME-induced MECLR inhibition could not be accounted for by a cytotoxic effect on epidermal Langerhans cells (LC), the class II major histocompatibility (MHC) antigen-bearing EC type that is fully responsible for alloantigen presentation in a primary allogeneic MECLR. Pretreatment with Leu-Leu-OME was found to inhibit the culture-induced increase in surface expression of HLA-DR molecules on LC. These findings suggest that in addition to its cytotoxic effect on cells containing high levels of dipeptidyl peptidase I, Leu-Leu-OME can also perturb alloantigen-presenting cells that are not killed by this agent by modulating HLA-D region antigen expression, perhaps through its capacity to neutralize acid compartments within cells. In addition, these studies support the notion that the culture-induced upregulation of class II MHC antigens on epidermal LC is functionally associated with the enhanced alloantigen-presenting capabilities that these cells display after short-term culture and suggest that newly synthesized class II antigens might be critical to the alloantigen-presenting cell capabilities of LC.
Simon
J C
JC
Department of Dermatology, University of Freiburg, Germany.
Thiele
D L
DL
Schöpf
E
E
Sontheimer
R D
RD
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007801:Langerhans Cells / Q000187:drug effects*; D008297:Male
D000276:Adjuvants, Immunologic; D004151:Dipeptides; D007166:Immunosuppressive Agents; C045139:leucyl-leucine-methyl ester