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

• Published in: Immunology 2000-10, Vol.101 (2), p.191-200
• Main Authors: Kapasi, K., Albert, S. E., Yie, S.‐M., Zavazava, N., Librach, C. L.
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal - immunology; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell Division - immunology; Cytokines - biosynthesis; Cytotoxicity, Immunologic - immunology; Dose-Response Relationship, Immunologic; Female; histocompatibility antigen HLA; Histocompatibility Antigens Class I - immunology; HLA Antigens - immunology; HLA-G Antigens; Humans; Immune Tolerance; Lymphocyte Culture Test, Mixed; Original; Placenta - immunology; Pregnancy; T-Lymphocytes, Cytotoxic - immunology; Th1 Cells - immunology; Th2 Cells - immunology
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1046/j.1365-2567.2000.00109.x

Summary Human leucocyte antigen (HLA) ‐G is expressed on trophoblast cells during pregnancy, suggesting a role in protection of the semiallogeneic fetus. Published data suggest that HLA‐G protects a cell against natural killer cell lysis. It has been hypothesized that HLA‐G may also protect the fetus by preventing allo‐cytotoxic T lymphocyte (CTL) responses. To test this hypothesis, we assayed the effects of various concentrations of purified HLA‐G on CTL response in a mixed lymphocyte culture (MLC) system. We found that concentrations ≥ 0·1 µg/ml of HLA‐G suppressed the allo‐CTL response by 30–100% over the control, but, paradoxically, concentrations of 0·01–0·05 µg/ml of HLA‐G augmented the allo‐CTL response by 25–50% over the control. Concentrations ≤ 0·001 µg/ml HLA‐G had no effect. Addition of HLA‐G to preprimed allo‐CTL effector cells did not affect their killing ability. Allo‐CTL suppressive doses of HLA‐G induced a T helper type 2 (Th2) cytokine response, whereas allo‐CTL‐enhancing doses 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 support a potential role for HLA‐G‐mediated suppression of allo‐CTL formation in normal pregnancies. In addition, the effects observed at lower concentrations of HLA‐G may have interesting implications for the condition of pre‐eclampsia in which concentrations of this HLA class I molecule are reduced.