hsBAFF regulates proliferation and response in cultured CD4(+) T lymphocytes by upregulation of intracellular free Ca(2+) homeostasis.
hsBAFF regulates proliferation and response in cultured CD4(+) T lymphocytes by upregulation of intracellular free Ca(2+) homeostasis.
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DOI：
10.1016/j.cyto.2010.11.006
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发表时间：
2011-02
期刊：
影响因子：
3.8
通讯作者：
L. Wen;S. Chen;Wei Zhang;Hong Ma;Shuang-quan Zhang;Long Chen
中科院分区：
文献类型：
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作者：
L. Wen;S. Chen;Wei Zhang;Hong Ma;Shuang-quan Zhang;Long Chen
B cell activating factor belonging to the TNF family (BAFF, also called BLyS, TALL-1, THANK, or zTNF4) is an important survival factor for B cells, and is able to regulate T-cell activation. Recently, we have demonstrated that treatment of mice with human soluble BAFF (hsBAFF) causes a significant increase of percentages of splenic CD4+T lymphocytes dose-dependently, but the CD8+T lymphocyte percentages maintained unchanged. Here, we show that hsBAFF significantly enhanced CD4+T lymphocyte response of cultured mouse splenic cells, and hsBAFF induced the proliferation and IL-2/IFN-γ secretion of purified CD4+T lymphocytes suboptimally stimulated through anti-CD3. Of importance, we observed that IL-2 or IFN-γ cytokine has additive effect on the proliferation and activity of hsBAFF-stimulated CD4+T lymphocytes. Using Flow cytometry with fluorescent probe, Fluo-3/AM, we found that hsBAFF elicited [Ca2+]ielevation contributing to CD4+T cell proliferation. This is evidenced by our finding that pretreatment with BAPTA/AM, an intracellular Ca2+chelator, significantly attenuated the proliferation of hsBAFF-stimulated CD4+T lymphocytes. Subsequently, we revealed that hsBAFF-stimulated CD4+T cell proliferation was markedly suppressed after pretreatment with EGTA, an extracellular Ca2+chelator, or with 2-APB, an inhibitor of Ca2+influx through CRAC channels, respectively, suggesting that extracellular Ca2+influx due to hsBAFF is closely associated with [Ca2+]ielevation contributing to CD4+T cell proliferation. In addition, we noticed that hsBAFF-treated cells conferred partial resistance to decrease of cellular viability induced by thapsigargin (Tg), an endoplasmic reticulum (ER) Ca2+-ATPase inhibitor. Taken together, our data indicate that hsBAFF may promote CD4+T cell proliferation and response by upregulation of [Ca2+]ihomeostasis.
