IL-15 controls T cell functions through its influence on CD30

PERIOLO NATALIA; GUILLÉN LAURA; ARRUVITO LOURDES; ALEGRE NS; NIVELONI; E; HWANG H; BAI JULIO; CHERÑAVSKY, ALEJANDRA

CYTOKINE.

ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD

Año: 2014 vol. 67 p. 44 - 51

1043-4666

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(+)CD25(high) 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.