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

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

Author information

1
Instituto de Inmunología, Genética y Metabolismo, Hospital de Clínicas "José de San Martín", Universidad de Buenos Aires, Buenos Aires, Argentina.
2
Sección Intestino Delgado, Departamento de Medicina, Hospital de Gastroenterología "Dr. Carlos Bonorino Udaondo", Buenos Aires, Argentina.
3
Instituto de Inmunología, Genética y Metabolismo, Hospital de Clínicas "José de San Martín", Universidad de Buenos Aires, Buenos Aires, Argentina. Electronic address: accher@fibertel.com.ar.

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.

KEYWORDS:

CD30; Celiac Disease; Interleukin-15; OX40; T cells

PMID:
24680481
DOI:
10.1016/j.cyto.2014.01.004
[Indexed for MEDLINE]

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