Soluble HLA-G influences the release of cytokines from allogeneic peripheral blood mononuclear cells in culture

• Published in: Molecular human reproduction Vol. 7; no. 2; pp. 195 - 200
• Main Authors: Kanai, T., Fujii, T., Kozuma, S., Yamashita, T., Miki, A., Kikuchi, A., Taketani, Y.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.02.2001; Oxford Publishing Limited (England)
• Subjects: Biological and medical sciences; Cell Line; cytokines; Cytokines - metabolism; Female; Fundamental and applied biological sciences. Psychology; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - metabolism; HLA Antigens - genetics; HLA Antigens - metabolism; HLA-G Antigens; Humans; Interferon-gamma - metabolism; Interleukin-10 - metabolism; Interleukin-3 - metabolism; Interleukin-4 - metabolism; Leukocytes, Mononuclear - immunology; Maternal-Fetal Exchange - immunology; membrane-bound HLA-G; Mother. Fetoplacental unit. Mammary gland. Milk; Pregnancy; Pregnancy Maintenance - immunology; Pregnancy. Parturition. Lactation; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; soluble HLA-G; Th1 Cells - immunology; Th2 Cells - immunology; Transfection; trophoblast; Tumor Necrosis Factor-alpha - metabolism; Vertebrates: reproduction; Human; Trophoblaste; Cell culture; Monocyte; Fetal membrane; Leukocyte; Cytokine; Soluble form; Gene expression; Allogeneic system; Antigen; Pregnancy; Plasma membrane; Exocrine secretion
• ISSN: 1360-9947; 1460-2407; 1460-2407
• DOI: 10.1093/molehr/7.2.195

Exquisitely regulated cytokine balance during early pregnancy is thought to be necessary for promoting survival of the fetal allograft. Our previous studies have demonstrated that membrane-bound human leukocyte antigen (mHLA-G) expressed on trophoblasts is one of the key factors in regulating cytokine balance by shifting the Th1/Th2 balance toward Th2 polarization, a favourable milieu for the maintenance of pregnancy. Given that trophoblasts secrete soluble HLA-G (sHLA-G), we examined its biological roles in comparison with mHLA-G. We cultured peripheral blood mononuclear cells (PBMC) with either the HLA-A and -B-deficient B lymphoblast cell line (721.221 cells) or the same cell line transfected with mHLA-G (721.221-G1 cells), in the presence or absence of recombinant sHLA-G. Cytokine concentrations in the culture media were determined by enzyme-linked immunosorbent assay. In contrast to mHLA-G protein, sHLA-G stimulated the release of tumour necrosis factor (TNF)-α and interferon (IFN)-γ, whereas it reduced the release of interleukin (IL)-3, regardless of the presence of the presence of a stimulatory effect of the mHLA-G-expressing cells. Although mHLA-G reduced the release of IL-4, sHLA-G did not have any effect. Conversely, sHLA-G stimulated the release of IL-10 whereas mHLA-G was without effect. These results suggest that sHLA-G regulates the release of cytokines from PBMC chiefly by counterbalancing mHLA-G, and thereby may play a role in maintaining pregnancy.