Increased production of soluble HLA-G molecules in stimulated peripheral blood mononuclear cells following extracorporeal photopheresis: is it a mechanism involved in the therapeutic effect of the procedure?
We hypothesized that the effects of extracorporeal photopheresis (ECP) are mediated by induction of immunosuppressive cytokines like IL-10, which enhances synthesis of HLA-G molecules. HLA-G products are expressed by CD14+ peripheral blood mononuclear cells (PBMC) and play an important role in inhibition of cell mediated immunity. ECP induces apoptosis in lymphocytes but not in CD14+ cells. We, therefore, investigated the concentrations both of IL-10 and of soluble HLA-G5/sHLA-G1 molecules in supernatants from cultures of lipopolysaccharide-stimulated PBMC obtained from leukocyte collection bags of 10 patients receiving ECP for graft versus host disease both before (pre-irradiation) and after (post-irradiation) exposure to 8-methoxypsoralen and UVA irradiation. Levels of both IL-10 and HLA-G5/sHLA-G1 molecules were increased in the post-irradiation cultures. This suggests that therapeutic effects of ECP could be mediated by increased production of IL-10 and tolerogenic HLA-G molecules.
Rizzo
Roberta
R
Department of Experimental and Diagnostic Medicine, Section of Medical Genetics, University of Ferrara, Ferrara, Italy. rbr@unife.it
Melchiorri
Loredana
L
Tazzari
Pier Luigi
PL
Tassi
Cristina
C
Soli
Maurizio
M
Lunghi
Monica
M
Belloni
Maurizio
M
Conte
Roberto
R
Baricordi
Olavio R
OR
D002478:Cells, Cultured; D006086:Graft vs Host Disease / Q000378:metabolism / Q000628:therapy*; D006680:HLA Antigens / Q000096:biosynthesis*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017893:Photopheresis
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D008070:Lipopolysaccharides; D016753:Interleukin-10