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Blood, 15 December 2004, Vol. 104, No. 13, pp. 4020-4028.
Prepublished online as a Blood First Edition Paper on August 10, 2004; DOI 10.1182/blood-2004-03-0885.


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IMMUNOBIOLOGY

Are interleukin-16 and thrombopoietin new tools for the in vitro generation of dendritic cells?

Silvia Della Bella, Stefania Nicola, Inna Timofeeva, Maria Luisa Villa, Armando Santoro, and Anna C. Berardi

From the Dipartimento di Scienze e Tecnologie Biomediche, Laboratorio di Immunologia, Università di Milano, Milan, Italy; Istituto Clinica Humanitas, Laboratorio di Ematologia/Oncologia, Rozzano, Milan, Italy; Ospedale Pediatrico Bambino Gesù, Laboratorio di Ricerche "Cellule Staminali," Rome, Italy.

The effects of interleukin 16 (IL-16) on dendritic cell (DC) generation from human CD34+ progenitor cells are not known. Here, we show that IL-16 added to a basal cocktail comprised of granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, Flt-3 ligand (Flt3L), and tumor necrosis factor {alpha} (TNF-{alpha}) does induce the CD34+ hematopoietic cells to proliferate in vitro and to differentiate into phenotypically and functionally mature DCs. IL-16 exerts this function more efficiently than stem cell factor (SCF) as a control, thrombopoietin (TPO), or IL-16 plus TPO. Moreover, we show that the combination of IL-16 plus TPO induces the generation of tolerogenic DCs, able to induce an anergic state in T cells that persists when T cells are rechallenged with immunogenic DCs. An altered pattern of cytokine production, a reduced expression of the C-type lectin DC-SIGN, and an increased surface expression of the inhibitory molecules immunoglobulin-like transcript 2 (ILT-2), ILT-3, and ILT-4 may all contribute to confer the tolerogenic properties of these DCs. Generation of tolerogenic DCs may aid the exploration of new therapeutic strategies to promote tolerance to autoantigens and prevent disease development. (Blood. 2004;104:4020-4028)


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