Soluble HLA-G inhibits human dendritic cell-triggered allogeneic T-cell proliferation without altering dendritic differentiation and maturation processes.
The role of the nonclassical human leukocyte antigen (HLA) class Ib molecule HLA-G in immune tolerance was first reported at maternofetal interface. This immunomodulating role could be exerted more generally in tumoral or post-transplantation situations in inhibiting natural killer (NK) and T-lymphocyte mediated lysis. Among the different transcripts resulting from alternative splicing, the mainly secreted isoform, HLA-G5, corresponds to complete molecule and has been demonstrated to be elevated in melanomas and in serum from heart-transplanted patients. As dendritic cells expressed ILT4, an inhibitory receptor capable of interacting with HLA-G, we have studied the effect of soluble HLA-G (HLA-G5) on differentiation, maturation, apoptosis and function of monocyte or CD34+-derived dendritic cells (DC). Soluble HLA-G did not alter differentiation, maturation or apoptosis of DC whatever their origin. On the other hand, an inhibitory effect of HLA-G5 on T lymphocytes proliferation was found in 53% of mixed leukocyte reactions (MLR) and was variable in intensity. These data demonstrate an indirect way of HLA-G5 action on DC occurring via T lymphocytes that reinforces the immune inhibitory role of soluble HLA-G capable to be secreted during tumoral malignancies or following heart transplantation.
Le Friec
Gaëlle
G
Laboratoire Universitaire d'Hématologie et de la Biologie des Cellules Sanguines, UPRES EA 22-33, Faculté de Médecine, Université de Rennes 1, Rennes, France.
Laupèze
Béatrice
B
Fardel
Olivier
O
Sebti
Yasmine
Y
Pangault
Céline
C
Guilloux
Valérie
V
Beauplet
Alain
A
Fauchet
Renée
R
Amiot
Laurence
L
D018952:Antigens, CD34 / Q000032:analysis; D017209:Apoptosis; D015153:Blotting, Western; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D006680:HLA Antigens / Q000235:genetics / Q000502:physiology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000502:physiology; D010641:Phenotype; D012995:Solubility; D013601:T-Lymphocytes / Q000502:physiology*
D018952:Antigens, CD34; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I