Ly9 (CD229)-deficient mice exhibit T cell defects yet do not share several phenotypic characteristics associated with SLAM- and SAP-deficient mice
Ly9 (CD229)-deficient mice exhibit T cell defects yet do not share several phenotypic characteristics associated with SLAM- and SAP-deficient mice
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DOI：
10.4049/jimmunol.176.1.291
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发表时间：
2006-01-01
影响因子：
4.4
通讯作者：
McKean, DJ
中科院分区：
文献类型：
--
作者：
Graham, DB;Bell, MP;McKean, DJ
信号淋巴细胞活化分子（SLAM）家族受体在调节先天性和适应性免疫应答中起关键作用。几种SLAM家族受体已被证明与衔接分子SAP相互作用;然而，随后的细胞内信号传导定义不清。值得注意的是，SLAM相关蛋白（SAP）的突变导致X连锁淋巴组织增生性疾病，这是一种罕见但致命的免疫缺陷。尽管已知SLAM家族成员Ly 9（CD 229）与SAP相互作用，但该受体的功能仍然难以捉摸。因此，我们产生了Ly 9（-/-）小鼠，并将它们的表型与SLAM（-/-）和SAP（-/-）小鼠的表型进行了比较。我们报道了Ly 9（-/-）T细胞在体外用抗TCR和抗CD 28刺激后表现出与IL-4产生减少相关的轻度Th 2缺陷。这种缺陷在程度上类似于先前报道的SLAM（-/-）小鼠中的Th 2缺陷，但比在SAP（-/-）小鼠中观察到的更微妙。与SLAM（-/-）和SAP（-/-）小鼠相反，Ly 9（-/-）小鼠的T细胞在体外用抗CD 3进行次优刺激后增殖较差并且产生很少的IL-2。我们还发现Ly 9（-/-）巨噬细胞在细胞因子产生或细菌杀伤方面没有表现出如在SLAM（-/-）巨噬细胞中观察到的缺陷。此外，Ly 9（-/-）小鼠与SAP（-/-）小鼠的不同之处在于，它们促进NKT细胞的正常发育，并对淋巴细胞性脉络丛脑膜炎病毒产生适当的T和B细胞应答。我们已经鉴定了Ly-9（-/-）小鼠与SLAM（-/-）和SAP（-/-）小鼠之间的显著表型差异。虽然Ly 9、SLAM和SAP在促进Th 2极化中发挥共同作用，但Ly-9独特地参与增强T细胞活化。
Signaling lymphocyte activation molecule (SLAM) family receptors are critically involved in modulating innate and adaptive immune responses. Several SLAM family receptors have been shown to interact with the adaptor molecule SAP; however, subsequent intracellular signaling is poorly defined. Notably, mutations in SLAM-associated protein (SAP) lead to X-linked lymphoproliferative disease, a rare but fatal immunodeficiency. Although the SLAM family member Ly9 (CD229) is known to interact with SAP, the functions of this receptor have remained elusive. Therefore, we have generated Ly9(-/-) mice and compared their phenotype with that of SLAM(-/-) and SAP(-/-) mice. We report that Ly9(-/-) T cells exhibit a mild Th2 defect associated with reduced IL-4 production after stimulation with anti-TCR and anti-CD28 in vitro. This defect is similar in magnitude to the previously reported Th2 defect in SLAM(-/-) mice but is more subtle than that observed in SAP(-/-) mice. In contrast to SLAM(-/-) and SAP(-/-) mice, T cells from Ly9(-/-) mice proliferate poorly and produce little IL-2 after suboptimal stimulation with anti-CD3 in vitro. We have also found that Ly9(-/-) macrophages exhibit no defects in cytokine production or bacterial killing as was observed in SLAM(-/-) macrophages. Additionally, Ly9(-/-) mice differ from SAP(-/-) mice in that they foster normal development of NKT cells and mount appropriate T and B cell responses to lymphocytic choriomeningitis virus. We have identified significant phenotypic differences between Ly-9(-/-) mice as compared with both SLAM(-/-) and SAP(-/-) mice. Although Ly9, SLAM, and SAP Play a common role in promoting Th2 polarization, Ly-9 is uniquely involved in enhancing T cell activation.