TY - JOUR
T1 - Effects of the immunosuppressive dipeptide L-leucyl-L-leucine O-methyl ester on epidermal Langerhans cells
AU - Simon, Jan C.
AU - Thiele, Dwain L
AU - Schöpf, E.
AU - Sontheimer, Rick D.
PY - 1992/11
Y1 - 1992/11
N2 - 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.
AB - 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.
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U2 - 10.1111/1523-1747.ep12669808
DO - 10.1111/1523-1747.ep12669808
M3 - Article
C2 - 1431239
AN - SCOPUS:0026442210
SN - 0022-202X
VL - 99
SP - 80
EP - 82
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 5
ER -