Characterization of adenosine deaminase binding to human CD26 on T cells and its biologic role in immune response.
Characterization of adenosine deaminase binding to human CD26 on T cells and its biologic role in immune response.
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DOI：
10.4049/jimmunol.156.4.1349
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发表时间：
1996-02
影响因子：
4.4
通讯作者：
R. Dong;J. Kameoka;M. Hegen;Takashi Tanaka;Y. Xu;S. Schlossman;C. Morimoto
中科院分区：
文献类型：
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作者：
R. Dong;J. Kameoka;M. Hegen;Takashi Tanaka;Y. Xu;S. Schlossman;C. Morimoto
CD26是一种T细胞活化型抗原，又称二肽基肽酶IV，与T细胞和T细胞系表面的腺苷脱氨酶(ADA)直接相关。在本研究中，我们研究了ADA和CD26的结合以及这种相互作用的功能后果。我们发现，在缺乏ADA或二肽基肽酶IV酶活性的T细胞系中，ADA与CD26相关，这表明二肽基肽酶IV与ADA之间的关联不需要酶活性。此外，利用免疫电子显微镜，我们证明CD26和ADA共定位于细胞表面，而不是细胞内，这表明CD26不能将ADA转运到细胞表面。为了与这一观察结果保持一致，我们发现，缺乏人ADA的人CD26转基因小鼠前B细胞系从细胞外来源获得ADA。更重要的是，腺苷在没有细胞表面ADA的情况下，抑制了各种刺激诱导的T细胞增殖和IL-2的产生。另一方面，细胞表面表达ADA和CD26的细胞对腺苷的抑制作用有更强的抵抗力。这些数据表明，细胞表面的ADA参与了一个重要的免疫调节机制，通过释放的ADA与细胞表面CD26结合，该复合体能够降低局部腺苷的浓度。
CD26, a T cell activation Ag, also known as dipeptidyl peptidase IV, is directly associated with adenosine deaminase (ADA) on the surface of T cells and T cell lines. In the present study, we examined both the binding of ADA and CD26 and the functional consequences of this interaction. We found that ADA was associated with CD26 on T cell lines lacking either ADA or dipeptidyl peptidase IV enzymatic activity, indicating that the association between dipeptidyl peptidase IV and ADA did not require enzymatic activity. Moreover, using immunoelectron microscopy, we demonstrated that CD26 and ADA co-localized on the cell surface, but not inside cells, suggesting that CD26 did not transport ADA to the surface. In keeping with this observation, we showed that human CD26-transfected murine pre-B cell lines lacking human ADA acquired ADA from an extracellular source. More importantly, adenosine in the absence of cell surface ADA inhibited T cell proliferation and IL-2 production induced by various stimuli. On the other hand, cells expressing ADA and CD26 on the surface were much more resistant to the inhibitory effect of adenosine. These data suggest that ADA on the cell surface is involved in an important immunoregulatory mechanism by which released ADA binds to cell surface CD26, and this complex is capable of reducing the local concentration of adenosine.