Expression of functional soluble human leucocyte antigen-G molecules in lymphoproliferative disorders.
Membrane-bound and soluble human leucocyte antigen-G (sHLA-G) molecules display immunotolerant properties favouring tumour cell escape from immune surveillance. sHLA-G molecules have been detected in several tumour pathologies; this study aimed to evaluate sHLA-G expression in lymphoproliferative disorders. sHLA-G plasma level was significantly increased in 110 of 178 newly diagnosed lymphoid proliferations cases i.e. 59% of chronic lymphocytic leukaemia, 65% of B non-Hodgkin lymphomas (NHL) and 58% of T-NHL. To assess the mechanisms involved in this secretion, the differential effect of cytokines was tested in in vitro cultures of NHL cells. A significant induction of sHLA-G level was shown in T-NHL in contrast with B-NHL and normal equivalent cells, after cytokine stimulation with (i) interferongamma (IFNgamma), interleukin-2 (IL-2) and granulocyte-macrophage colony-stimulating factor, (ii) IL-10 and (iii) transforming growth factor beta. An impact of microenvironment on sHLA-G expression was found in B-NHL as shown by the in vitro effect of addition of normal monocytes. Finally, a functional effect of sHLA-G molecules purified from pathologic plasma was demonstrated by their strong capacity to inhibit T-cell proliferation at concentrations currently observed during these disorders. These results suggest that functional sHLA-G molecules are upregulated in lymphoproliferative disorders which can support their potential immunomodulatory role during this pathology.
Sebti
Yasmine
Y
UPRES Immunologie Hématologie, Université de Rennes 1, Rennes, France.
Le Maux
Amélie
A
Gros
Frédéric
F
De Guibert
Sophie
S
Pangault
Céline
C
Rouas-Freiss
Nathalie
N
Bernard
Marc
M
Amiot
Laurence
L
D001402:B-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006680:HLA Antigens / Q000097:blood*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000097:blood*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007378:Interleukins / Q000276:immunology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology; D016399:Lymphoma, T-Cell / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology; D014407:Tumor Cells, Cultured
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D007378:Interleukins; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor