Regulation of murine lymphokine production in vivo. III. The lymphoid tissue microenvironment exerts regulatory influences over T helper cell function.
Regulation of murine lymphokine production in vivo. III. The lymphoid tissue microenvironment exerts regulatory influences over T helper cell function.
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DOI：
10.1084/jem.171.4.979
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发表时间：
1990-04-01
期刊：
影响因子：
--
通讯作者：
Dudley D
中科院分区：
文献类型：
--
作者：
Daynes RA;Araneo BA;Dowell TA;Huang K;Dudley D
我们研究了从正常或抗原免疫供者的不同淋巴器官中分离的小鼠T淋巴细胞在抗CD3或特异性抗原激活后产生IL-2或IL-4的能力。我们的结果表明，淋巴器官中的T细胞被非粘膜组织部位(如腋窝、腹股沟、臂淋巴结或脾)引流，激活后产生作为主要T细胞生长因子(TCGF)的IL-2。相反，来自淋巴器官的活化T细胞被粘膜组织(Peyer‘s Patch，以及颈部、腹主动脉周围和旁腺淋巴结)引流，产生IL-4，作为TCGF的主要种类。对来自同基因供者提供的抗原免疫淋巴细胞过继接受者的淋巴组织的分析提供了证据，证明T细胞在特定的淋巴间隔内停留期间受到直接影响。这些淋巴组织的影响似乎改变了常驻T细胞产生不同种类TCGF的潜力。类固醇激素是已知的特定细胞基因的转录增强和抑制因子，参与了对TCGF产生的控制机制。糖皮质激素(GCs)对所有循环的T细胞都有全身性作用，表现为GC处理小鼠所有淋巴器官的T细胞产生IL-4的优势明显，或在用T细胞有丝分裂原激活细胞之前，将正常淋巴细胞在体外直接暴露于GCs。此外，雄激素类固醇DHEA似乎对T细胞通过外周淋巴器官的运输提供了表观遗传影响。这种类固醇的影响导致激活后IL-2分泌的可能性增强。DHEA促进的影响的解剖区划似乎是由淋巴组织中不同水平的DHEA-硫酸酯酶介导的。DHEA-硫酸酯酶是一种能够将DHEA-硫酸盐(非活性)转化为活性荷尔蒙DHEA的酶。我们发现这种酶在小鼠巨噬细胞中具有很高的活性。我们的发现对免疫生物学的影响是非常大的，并表明T细胞虽然克隆性地限制了抗原肽的识别，但对于它们激活后产生的淋巴因子的种类似乎也表现出了极大的灵活性。这一高度保守的机制的调节似乎部分(如果不完全)是由不同种类的类固醇激素施加的细胞影响所控制的，这些激素分别以内分泌或旁分泌的方式提供，分别介导全身或组织局部的影响。
We investigated the capacity of murine T lymphocytes, isolated from various lymphoid organs of normal or antigen-primed donors, to produce IL-2 or IL-4 after activation with anti-CD3 or specific antigen. Our results established that T cells resident within lymphoid organs being drained by nonmucosal tissue sites (e.g., axillary, inguinal, brachial lymph nodes, or spleen) produced IL-2 as the predominant T cell growth factor (TCGF) after activation. Conversely, activated T cells from lymphoid organs being drained by mucosal tissues (Peyer's patches, and cervical, periaortic, and parathymic lymph nodes) produced IL-4 as the major species of TCGF. Analysis of the lymphoid tissues obtained from adoptive recipients of antigen-primed lymphocytes provided by syngeneic donors provided evidence that direct influences were being exerted on T cells during their residence within defined lymphoid compartments. These lymphoid tissue influences appeared to be responsible for altering the potential of resident T cells to produce distinct species of TCGF. Steroid hormones, known transcriptional enhancers and repressors of specific cellular genes, were implicated in the controlling mechanisms over TCGF production. Glucocorticoids (GCs) were found to exert a systemic effect on all recirculating T cells, evidenced by a marked dominance in IL-4 production by T cells obtained from all lymphoid organs of GC-treated mice, or after a direct exposure of normal lymphoid cells to GCs in vitro before cellular activation with T cell mitogens. Further, the androgen steroid DHEA appeared to be responsible for providing an epigenetic influence to T cells trafficking through peripheral lymphoid organs. This steroid influence resulted in an enhanced potential for IL-2 secretion after activation. Anatomic compartmentalization of the DHEA-facilitated influence appears to be mediated by differential levels of DHEA-sulfatase in lymphoid tissues. DHEA-sulfatase is an enzyme capable of converting DHEA-sulfate (inactive) to the active hormone DHEA. We find very high activities of this enzyme isolated in murine macrophages. The implications of our findings to immunobiology are very great, and indicate that T cells, while clonally restricted for antigen peptide recognition, also appear to exhibit an extreme flexibility with regards to the species of lymphokines they produce after activation. Regulation of this highly conservative mechanism appears to be partially, if not exclusively, controlled by cellular influences being exerted by distinct species of steroid hormones, supplied in an endocrine or a paracrine manner where they mediate either systemic or tissue-localized influences, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
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影响因子：
64.8
作者：
GALLATIN, WM;WEISSMAN, IL;BUTCHER, EC
通讯作者：
BUTCHER, EC
影响因子：
5.4
作者：
KARASUYAMA, H;MELCHERS, F
通讯作者：
MELCHERS, F
DOI：
10.1084/jem.153.5.1198
发表时间：
1981-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kappler JW;Skidmore B;White J;Marrack P
通讯作者：
Marrack P
影响因子：
5.4
作者：
HENDRIKS, HR;EESTERMANS, IL
通讯作者：
EESTERMANS, IL
影响因子：
56.9
作者：
EVANS, RM
通讯作者：
EVANS, RM