HLA-G has a concentration-dependent effect on the generation of an allo-CTL response

Human leucocyte antigen (HLA) -G is expressed on trophoblast cells during p regnancy, suggesting a role in protection of the semiallogeneic fetus. Publ ished data suggest that HLA-G protects a cell against natural killer cell l ysis. It has been hypothesized that HLA-G may also protect the fetus by pre venting allo-cytotoxic T lymphocyte (CTL) responses. To test this hypothesi s, we assayed the effects of various concentrations of purified HLA-G on CT L response in a mixed lymphocyte culture (MLC) system. We found that concen trations greater than or equal to 0.1 mu g/ml of HLA-G suppressed the allo- CTL response by 30-100% over the control, but, paradoxically, concentration s of 0.01-0.05 mu g/ml of HLA-G augmented the allo-CTL response by 25-50% o ver the control. Concentrations less than or equal to 0.001 mu g/ml HLA-G h ad no effect. Addition of HLA-G to preprimed allo-CTL effector cells did no t affect their killing ability. Allo-CTL suppressive doses of HLA-G induced a T helper type 2 (Th2) cytokine response, whereas allo-CTL-enhancing dose s of HLA-G induced a Th1-type cytokine response. HLA-G purified from first- trimester placenta does not affect allo-proliferative responses nor does it alter the percentage of CD4(+) or CD8(+) T cells in MLCs. These findings s upport a potential role for HLA-G-mediated suppression of allo-CTL formatio n in normal pregnancies. In addition, the effects observed at lower concent rations of HLA-G may have interesting implications for the condition of pre -eclampsia in which concentrations of this HLA class I molecule are reduced .