Spaner David E, Hammond Caitlin, Mena Jenny, Shi Yonghong
Division of Molecular and Cellular Biology, Research Institute, Sunnybrook and Women's College Health Sciences Center, Toronto M4N 3M5, Canada.
Br J Haematol. 2004 Dec;127(5):531-42. doi: 10.1111/j.1365-2141.2004.05240.x.
Weak immunogenicity of chronic lymphocytic leukaemia (CLL) cells may contribute to disease progression and inhibit the effectiveness of immunotherapies, such as vaccines. Agents that can enhance the antigen presenting capabilities of CLL cells might then help to improve the clinical results of immunotherapies. This study investigated the effects of the common gamma chain-binding cytokines, interleukin (IL)-2 and IL-15, on costimulatory properties of primary CLL cells from 51 patients. IL-2 improved the ability of CLL cells to stimulate T cell proliferation and increased the expression of costimulatory molecules (particularly CD80) in a dose-dependent fashion, especially in CLL cells with weak expression of CD38. CD80 and CD86 induction by IL-2 were positively regulated through the mitogen-activated protein kinase pathway, while CD86 expression was negatively regulated through Janus kinase pathways. However, further activation with protein kinase C agonists was required for IL-2 activated CLL cells to stimulate autologous T cells sufficiently to clear bystander CLL cells from mixed lymphocyte responses. IL-15 had similar effects on the costimulatory properties of CLL cells. These results suggest a role for IL-2, or IL-15, in immunotherapeutic strategies for CLL.
慢性淋巴细胞白血病（CLL）细胞的弱免疫原性可能导致疾病进展，并抑制免疫疗法（如疫苗）的有效性。能够增强CLL细胞抗原呈递能力的药物可能有助于改善免疫疗法的临床效果。本研究调查了常见的γ链结合细胞因子白细胞介素（IL）-2和IL-15对51例患者原代CLL细胞共刺激特性的影响。IL-2改善了CLL细胞刺激T细胞增殖的能力，并以剂量依赖的方式增加了共刺激分子（特别是CD80）的表达，尤其是在CD38表达较弱的CLL细胞中。IL-2诱导的CD80和CD86通过丝裂原活化蛋白激酶途径受到正调控，而CD86的表达通过Janus激酶途径受到负调控。然而，IL-2激活的CLL细胞需要用蛋白激酶C激动剂进一步激活，才能充分刺激自体T细胞以清除混合淋巴细胞反应中的旁观者CLL细胞。IL-15对CLL细胞的共刺激特性有类似影响。这些结果表明IL-2或IL-15在CLL的免疫治疗策略中发挥作用。
