Sivasankar Baalasubramanian, Longhi M Paula, Gallagher Kathleen M E, Betts Gareth J, Morgan B Paul, Godkin Andrew J, Gallimore Awen M
Department of Medical Biochemistry and Immunology, Henry Wellcome Building, School of Medicine, Cardiff University, Heath Park, Cardiff, UK.
J Immunol. 2009 May 1;182(9):5203-7. doi: 10.4049/jimmunol.0804243.
CD59, a broadly expressed GPI-anchored molecule, regulates formation of the membrane attack complex of the complement cascade. We previously demonstrated that mouse CD59 also down-modulates CD4(+) T cell activity in vivo. In this study, we explored the role of CD59 on human CD4(+) T cells. Our data demonstrate that CD59 is up-regulated on activated CD4(+) T cells and serves to down-modulate their activity in response to polyclonal and Ag-specific stimulation. The therapeutic potential of this finding was explored using T cells isolated from colorectal cancer patients. The findings were striking and indicated that blockade of CD59 significantly enhanced the CD4(+) T cell response to two different tumor Ags. These data highlight the potential for manipulating CD59 expression on T cells for boosting weak immune responses, such as those found in individuals with cancer.
CD59是一种广泛表达的糖基磷脂酰肌醇（GPI）锚定分子，可调节补体级联反应的膜攻击复合物的形成。我们之前证明，小鼠CD59在体内也会下调CD4(+) T细胞活性。在本研究中，我们探究了CD59对人CD4(+) T细胞的作用。我们的数据表明，活化的CD4(+) T细胞上CD59表达上调，并在多克隆和抗原特异性刺激下下调其活性。利用从结直肠癌患者分离的T细胞探究了这一发现的治疗潜力。结果令人惊讶，表明阻断CD59可显著增强CD4(+) T细胞对两种不同肿瘤抗原的反应。这些数据凸显了通过操纵T细胞上CD59的表达来增强微弱免疫反应（如癌症患者体内的免疫反应）的潜力。
