白细胞介素-15通过影响乳糜泻中的CD30和OX40抗原控制T细胞功能。

IL-15 controls T cell functions through its influence on CD30 and OX40 antigens in Celiac Disease.

作者信息

Periolo N, Guillén L, Arruvito M L, Alegre N S, Niveloni S I, Hwang J H, Bai J C, Cherñavsky A C

机构信息

Instituto de Inmunología, Genética y Metabolismo, Hospital de Clínicas "José de San Martín", Universidad de Buenos Aires, Buenos Aires, Argentina.

Sección Intestino Delgado, Departamento de Medicina, Hospital de Gastroenterología "Dr. Carlos Bonorino Udaondo", Buenos Aires, Argentina.

出版信息

Cytokine. 2014 May;67(1):44-51. doi: 10.1016/j.cyto.2014.01.004. Epub 2014 Mar 14.

DOI:10.1016/j.cyto.2014.01.004

PMID:24680481

Abstract

AIM

To evaluate the ability of interleukin (IL)-15 to control T cell functions through its influence on CD30 and OX40 expressing cells in Celiac Disease (CD). In peripheral blood (PB), by examining the expression of OX40 in conventional effectors cells and T cells with a phenotypic specialization of regulatory cells [CD4+CD25high forkhead box protein 3 (Foxp3)+], and the co stimulation of IFN-γ and IL-4 production within CD30 and OX40 positive subsets of T cells. At the duodenal mucosa, by assessing the expression of CD30 and OX40 in intraepithelial (IE) and lamina propria (LP) lymphocytes (IEL, LPL).

PATIENTS AND METHODS

PB and duodenal mucosal biopsies were obtained from 38 patients with classic CD (Cel) and 38 healthy controls (HC). Analysis of cell surface and/or intracellular antigens was performed in anti-CD3-treated PB mononuclear cells (PBMC) before and after treatment with recombinant IL-15 (rIL-15), and in IE and LP cellular suspensions prepared from duodenal biopsies pre-treated with/without rIL-15.

RESULTS

A subpopulation of CD3+OX40+ T blasts was induced in Cel and HC by a 3days treatment of PBMC with anti-CD3 and decreased its size thereafter, regardless of the presence of rIL-15. However, the addition of rIL-15 to T blasts distinctively induced the survival of T cells with a regulatory phenotype that expresses OX40 antigen in Cel (p<0.05). Celiac patients showed higher frequencies of IFN-γ-producing CD3+CD30+ blasts before and after treatment with rIL-15 (p<0.05, vs. HC). IL-15 increased the frequencies of CD3+CD30+ LPL (HC: p<0.05, Cel: p<0.05) but not of CD3+OX40+ LPL, and CD30 or OX40 positive IEL.

CONCLUSIONS

The distinctive control of OX40+ cells with a T regulatory phenotype mediated by the influence of IL-15 comes out as new function of this cytokine in the context of CD. The higher production of IFN-γ by a subpopulation of peripheral CD3+CD30+ cells contributes to the type I biased immune response.

摘要

目的

评估白细胞介素（IL）-15通过影响乳糜泻（CD）中表达CD30和OX40的细胞来控制T细胞功能的能力。在外周血（PB）中，通过检测常规效应细胞和具有调节细胞表型特征的T细胞[CD4+CD25高叉头框蛋白3（Foxp3）+]中OX40的表达，以及T细胞CD30和OX40阳性亚群内IFN-γ和IL-4产生的共刺激。在十二指肠黏膜，通过评估上皮内（IE）和固有层（LP）淋巴细胞（IEL、LPL）中CD30和OX40的表达。

患者和方法

从38例经典CD患者（Cel）和38例健康对照者（HC）获取PB和十二指肠黏膜活检组织。在用重组IL-15（rIL-15）处理前后，对经抗CD3处理的PB单核细胞（PBMC）进行细胞表面和/或细胞内抗原分析，并对用/不用rIL-15预处理的十二指肠活检组织制备的IE和LP细胞悬液进行分析。

结果

用抗CD3处理PBMC 3天可在Cel和HC中诱导出一群CD3+OX40+T母细胞，此后其大小减小，无论是否存在rIL-15。然而，向T母细胞中添加rIL-15可显著诱导Cel中具有调节表型且表达OX40抗原的T细胞存活（p<0.05）。乳糜泻患者在用rIL-15处理前后，产生IFN-γ的CD3+CD30+母细胞频率更高（与HC相比，p<0.05）。IL-15增加了CD3+CD30+LPL的频率（HC：p<0.05，Cel：p<0.05），但未增加CD3+OX40+LPL以及CD30或OX40阳性IEL的频率。