Expression of functional soluble human leucocyte antigen-G molecules in lymphoproliferative disorders

Br J Haematol. 2007 Jul;138(2):202-12. doi: 10.1111/j.1365-2141.2007.06647.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / immunology
  • Cell Division / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • HLA Antigens / blood*
  • HLA-G Antigens
  • Histocompatibility Antigens Class I / blood*
  • Humans
  • Interferon-gamma / immunology
  • Interleukins / immunology
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Lymphoma, B-Cell / immunology
  • Lymphoma, T-Cell / immunology
  • Lymphoproliferative Disorders / immunology*
  • Monocytes / immunology
  • Prospective Studies
  • T-Lymphocytes / immunology
  • Transforming Growth Factor beta / immunology
  • Tumor Cells, Cultured

Substances

  • HLA Antigens
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • Interleukins
  • Transforming Growth Factor beta
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor