P40 molecule regulates NK cell activation mediated by NK receptors for HLA class I antigens and TCR-mediated triggering of T lymphocytes
P40 molecule regulates NK cell activation mediated by NK receptors for HLA class I antigens and TCR-mediated triggering of T lymphocytes
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DOI：
10.1093/intimm/9.9.1271
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发表时间：
1997-09-01
影响因子：
4.4
通讯作者：
Moretta, L
中科院分区：
文献类型：
--
作者：
Poggi, A;Tomasello, E;Moretta, L
p40先前被描述为一种能够抑制自然和cd16介导的NK细胞毒性的调节分子，在本研究中，我们分析了p40分子参与通过激活HLA i类特异性NK受体（NKR）诱导的NK细胞触发或对TCR α β介导的T细胞激活的影响。CD3（-）、CD16(+) NK细胞克隆表达活化的NKR (CD94或p50)，使用P815靶细胞和适当的单抗，在重定向杀伤实验中进行分析，在单独存在抗NKR或抗CD16单抗的情况下，检测到强烈的靶细胞裂解。添加抗p40单抗可强烈抑制抗nkr或抗cd16单抗诱导的细胞溶解。对CD45或淋巴细胞功能相关抗原-1特异性的单抗在同一实验系统中没有发挥任何抑制作用，激活CD94或p50的单抗交联诱导的游离细胞内钙（[Ca2+](i)）的增加被p40分子同时参与抑制，但不包括其他NK表面分子包括CD44和CD56。此外，p40分子交联强烈抑制cd94诱导的肿瘤坏死因子- α和ifn - γ的产生。对TCR α - β或γ - δ T细胞克隆的分析表明，p40分子与特异性单抗的结合，只对抗v - β（而不是抗v - δ或抗cd3）单抗诱导的细胞毒性有一定程度的抑制作用，另一方面，p40分子的结合可以阻止抗v (β)8或抗v (δ)2单抗诱导的T细胞增殖，对il -2诱导的NK细胞增殖也有类似的抑制作用。我们目前的研究结果表明，p40可能在NK和T淋巴细胞活化和增殖的调节中发挥作用。
p40 was previously described as a regulatory molecule capable of inhibiting both the natural and the CD16-mediated cytotoxicity of NK cells, In this study, we analyze the effect of p40 molecule engagement on the NK cell triggering induced by activating HLA class I-specific NK receptors (NKR) or on TCR alpha beta-mediated T cell activation. CD3(-)CD16(+) NK cell clones expressing activating NKR (either CD94 or p50) were analyzed in a redirected killing assay using P815 target cells and appropriate mAb, A strong target cell lysis was detected in the presence of anti-NKR or anti-CD16 mAb alone. Addition of anti-p40 mAb resulted in a strong inhibition of both anti-NKR or anti-CD16 mAb-induced cytolysis. mAb specific for either CD45 or lymphocyte function associated antigen-1 did not exert any inhibitory effect in the same experimental system, Free intracellular calcium ([Ca2+](i)) increase induced by mAb cross-linking of activating CD94 or p50 was inhibited by simultaneous engagement of p40 molecules, but not of other NK surface molecules including CD44 and CD56, In addition, cross-linking of p40 molecules strongly inhibited the CD94-induced tumor necrosis factor-alpha and IFN-gamma production. Analysis of TCR alpha beta or gamma delta T cell clones revealed that the engagement of p40 molecules, using specific mAb, induced some degree of inhibition only on anti-V-beta (but not anti-V-delta or anti-CD3) mAb-induced cytotoxicity, On the other hand, the p40 molecule engagement prevented T cell proliferation induced by either anti-V(beta)8 or anti-V(delta)2 mAb, A similar inhibitory effect was found on the IL-2-induced NK cell proliferation, Taken together, our present findings suggest that p40 may play a role in the regulation of NK and T lymphocyte activation and proliferation.