POLARIZED EXPRESSION OF CYTOKINES IN CELL CONJUGATES OF HELPER T-CELLS AND SPLENIC B-CELLS
POLARIZED EXPRESSION OF CYTOKINES IN CELL CONJUGATES OF HELPER T-CELLS AND SPLENIC B-CELLS
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DOI：
10.1073/pnas.88.3.775
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发表时间：
1991-02-01
影响因子：
11.1
通讯作者：
KUPFER, H
中科院分区：
文献类型：
--
作者：
KUPFER, A;MOSMANN, TR;KUPFER, H
我们通过双免疫荧光显微镜描述了克隆辅助 T 细胞与静息脾 B 细胞长时间相互作用过程中产生的四种细胞因子的细胞内定位。当两个兔免疫球蛋白特异性辅助 T 细胞克隆单独或一起与脾 B 细胞在抗原兔抗小鼠免疫球蛋白抗体存在下混合时，最多 29 小时后即可看到稳定的 T 细胞-B 细胞缀合物。对这些细胞的显微镜观察显示，其中一个 T 细胞克隆内的干扰素 γ 和白细胞介素 2 以及另一个 T 细胞克隆内的白细胞介素 4 和 5 集中在非常靠近 T 细胞与 B 细胞接触区域的位置。在 T 细胞与 B 细胞相互作用之前，细胞因子在 T 细胞中未见，并且它们的产生是严格抗原特异性的。这些研究表明，在单细胞水平上，辅助 T 细胞克隆可以与脾 B 细胞结合足够长的时间，以便 T 细胞产生细胞因子，细胞因子在结合的 B 细胞附近合成。我们认为细胞因子的极化合成可能导致它们向结合的 B 细胞定向分泌。通过在接触的 T 细胞-B 细胞膜（T 细胞和 B 细胞表面受体接合并聚集）处局部分泌非抗原特异性细胞因子，辅助 T 细胞可以诱导选择性和特异性 B 细胞反应。
We describe the intracellular localization, by double immunofluorescence microscopy, of four cytokines that were produced during the prolonged interaction of cloned helper T cells with resting splenic B cells. When two rabbit immunoglobulin-specific helper-T-cell clones were mixed, either separately or together, with splenic B cells in the presence of the antigen rabbit anti-mouse immunoglobulin antibodies, stable T-cell-B-cell conjugates were seen up to 29 hr later. Microscopic observations of these cells revealed that interferon-gamma and interleukin 2, inside one of the T-cell clones, and interleukins 4 and 5, inside the other T-cell clone, were concentrated very close to the T-cell-B-cell contact area. The cytokines were not seen in the T cells prior to their interaction with the B cells and their production was strictly antigen-specific. These studies show, at the single-cell level, that helper-T-cell clones can remain bound to splenic B cells long enough for the T cells to produce cytokines, which are synthesized near the bound B cells. We propose that the polarized synthesis of the cytokines may result in their directed secretion toward the bound B cells. By locally secreting the cytokines, which are not antigen-specific, at the contacting T-cell-B-cell membranes, where T- and B-cell surface receptors are engaged and clustered, the helper T cells can induce selective and specific B-cell responses.