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

We recently reported that the nonclassical HLA class I molecule HLA-G was e xpressed 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 react ion. Carrying out mixed lymphocyte cultures in which the responder cell pop ulation was depleted either in CD4(+) or CD8(+) T cells, we found that solu ble HLA-G5 protein but not the membrane-bound HLA-G isoform was secreted by allo-specific CD4(+) T cells from the responder population, which suppress ed the allogeneic proliferative T cell response. This inhibition may be rev ersed 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.