CD30 Is Required for CCL21 Expression and CD4 T Cell Recruitment in the Absence of Lymphotoxin Signals
CD30 Is Required for CCL21 Expression and CD4 T Cell Recruitment in the Absence of Lymphotoxin Signals
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DOI：
10.4049/jimmunol.0803481
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发表时间：
2009-04-15
影响因子：
4.4
通讯作者：
Lane, Peter J. L.
中科院分区：
文献类型：
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作者：
Bekiaris, Vasileios;Gaspal, Fabrina;Lane, Peter J. L.
淋巴组织诱导细胞表达多种肿瘤坏死家族配体，包括那些结合CD30和淋巴毒素13受体的配体。这两个信号通路都与脾中的B/T分离有关。在这项研究中，我们分析了一个淋巴毒素依赖的CD30信号，用于诱导T区趋化因子CCL21的表达。由于CD30缺乏导致CCL21的表达减少：淋巴毒素和CD30(DKO)信号缺乏的小鼠在其脾白髓区域的淋巴细胞聚集显著减少，没有T细胞局灶性聚集的证据。此外，与野生型或淋巴毒素缺乏的小鼠相比，dKO小鼠对野生型CD4T细胞的募集能力较差。系统发育分析表明，CD30信号早于淋巴毒素0受体。我们认为，来自淋巴组织诱导细胞的CD30信号是招募和激活CD4T细胞的原始机制。这将是高度组织化的淋巴毒素依赖的B和T白髓区域进化的垫脚石，在这些区域中，现在发展出CD4依赖的记忆抗体反应。免疫学杂志，2009,182：4771-4775。
Lymphoid tissue inducer cells express a diverse array of tumor necrosis family ligands, including those that bind CD30 and the lymphotoxin 13 receptor. Both of these signaling pathways have been linked with B/T segregation in the spleen. In this study, we have dissected a lymphotoxin-independent CD30-dependent signal for the induction of expression of the T zone chemokine, CCL21. Reduced expression of CCL21 due to CD30 deficiency was functionally significant: mice deficient in both lymphotoxin and CD30 (dKO) signals had significantly smaller accumulations of lymphocytes in their splenic white pulp areas, with no evidence of focal aggregation of T cells. Furthermore, recruitment of wild-type CD4 T cells was poor in dKO mice compared with both wild-type or lymphotoxin-deficient mice. Phylogeny suggests that CD30 signals predated those through the lymphotoxin 0 receptor. We suggest that CD30 signals from lymphoid tissue inducer cells were a primitive mechanism to recruit and prime CD4 T cells. This would have been a stepping stone in the evolution of the highly organized lymphotoxin dependent B and T white pulp areas within which CD4-dependent memory Ab responses now develop. The Journal of Immunology, 2009, 182: 4771-4775.