Soluble HLA-G protein secreted by allo-specific CD4+ T cells suppresses the allo-proliferative response: A CD4+ T cell regulatory mechanism

doi:10.1073/pnas.201407398

Soluble HLA-G protein secreted by allo-specific CD4⁺ T cells suppresses the allo-proliferative response: A CD4⁺ T cell regulatory mechanism

^*Service de Recherches en Hémato-Immunologie, Commissariat à l'Energie Atomique, Direction des Sciences du Vivant, Départment de Recherche Médicale, Hôpital Saint-Louis, 1 Avenue Claude-Vellefaux, 75010 Paris, France; ^†Laboratory for the Study of Cardiac Grafts and Prostheses, University Pierre et Marie Curie, Hôpital Broussais, 96 Rue Didot, 75014 Paris, France; ^‡Centre d'Étude du Polymorphisme Humain, Fondation Jean Dausset, 27 Rue Juliette Dodou, 75010 Paris, France; and ^§Department of Cardiovascular Surgery and Organ Transplantation, Georges Pompidou Hospital, 75015 Paris, France

Contributed by Jean Dausset

Abstract

We recently reported that the nonclassical HLA class I molecule HLA-G was expressed in the endomyocardial biopsies and sera of 16% of heart transplant patients studied. The aim of the present report is to identify cells that may be responsible for HLA-G protein expression during the allogeneic reaction. Carrying out mixed lymphocyte cultures in which the responder cell population was depleted either in CD4⁺ or CD8⁺ T cells, we found that soluble HLA-G5 protein but not the membrane-bound HLA-G isoform was secreted by allo-specific CD4⁺ T cells from the responder population, which suppressed the allogeneic proliferative T cell response. This inhibition may be reversed by adding the anti-HLA-G 87G antibody to a mixed lymphocyte culture. That may indicate a previously uncharacterized regulatory mechanism of CD4⁺ T cell proliferative response.

Footnotes

↵ ¶ To whom reprint requests should be addressed. E-mail: carosella{at}dsvidf.cea.fr.
Abbreviations:

PBMC,

peripheral blood mononuclear cell;

MLR,

mixed lymphocyte reaction