Soluble HLA-G molecules are increased in lymphoproliferative disorders.
The immunomodulatory properties of soluble human leukocyte antigen G (sHLA-G) explain its potential interest in malignancies. HLA-G frequently transcribed in lymphoproliferative disorders is rarely expressed at cell surface. In this article, we will demonstrate that the plasmatic level of soluble HLA-G was significantly increased in 70% of B chronic lymphocytic leukemia, 53% of non-Hodgkin B lymphoma (B-NHL), and 45% of T-NHL. To explain this variable secretion, the HLA-G secreting cell was searched and was identified as tumoral T4 lymphocytes only in one patient with Sezary syndrome. To approach the mechanisms involved in sHLA-G secretion, the potential role of cytokines has been studied in vitro on T lymphomas. A significant increase of sHLA-G level is observed after activation by cytokines associated with a small increase in the quantity of transcripts using real-time polymerase chain reaction, suggesting an involvement of both transcriptional and post-transcriptional mechanisms. Western Blot analysis reveals no evident variation of the protein expression whatever the conditions, suggesting a continuous secretion and a low intracellular storage. The frequency of the sHLA-G secretion associated to its inhibiting role on T cells and natural killer cells during tumoral lymphoid malignancies suggests a potential role of these molecules as escape mechanism from antitumoral response.
Sebti
Yasmine
Y
Laboratoire Universitaire d'Hématologie et la Biologie des Cellules Sanguines, UPRES EA 22 33, Faculté de Médecine, Université de Rennes 1, Rennes, France.
Le Friec
Gaëlle
G
Pangault
Céline
C
Gros
Frédéric
F
Drénou
Bernard
B
Guilloux
Valérie
V
Bernard
Marc
M
Lamy
Thierry
T
Fauchet
Renée
R
Amiot
Laurence
L
D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006680:HLA Antigens / Q000097:blood* / Q000235:genetics / Q000276:immunology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000097:blood* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000276:immunology*; D016399:Lymphoma, T-Cell / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012751:Sezary Syndrome / Q000276:immunology; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology; D014158:Transcription, Genetic; D019139:Tumor Escape
D000911:Antibodies, Monoclonal; D016207:Cytokines; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger