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[HLA-G: immune tolerance in normal and pathological physiology]
M Le Discorde1, P Moreau, N Rouas-Freiss
1Service de recherches en hémato-immunologie, CEA, DSV/DRM, hôpital Saint-Louis, institut d'hématologie, 1, avenue Claude Vellefaux, 75475 Paris, France.
Abstract:
HLA-G is a low polymorphic non-classical major histocompatibility complex class I molecule which can be expressed upon seven isoforms, and whose expression is correlated to immune tolerance situations. Indeed, the expression of HLA-G may allow partially or non histocompatible cells to escape host's immune aimed to eliminate these "foreign" cells. Functions share by HLA-G molecules are the ability to inhibit lysis mediated by natural killer (NK) and by cytotoxic T cells, and to induce apoptosis of activated CD8+ T cells via the HLA-G soluble form. Such model which evades defenses of the immune system was described in the foeto-maternal symbiosis, in tumoral cells or histo-incompatible graft previously. The importance of the role of HLA-G molecules expressed by particular cells as a shield against immune defenses is actually largely studied. The control of HLA-G expression could be used as immunotherapeutic approach, either by up-modulating HLA-G expression in order to favour tolerance of incompatible cells such as foetal cell or graft, or by down-modulating HLA-G expression in order to support the destruction of tumoral cells by cytotoxic T cells. This article reports the recent data on polymorphism, HLA-G gene transcription and implication of HLA-G molecules in immune responses during pregnancy, transplantation or tumoral growth.