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J Clin Immunol. 2010 Sep;30(5):659-68. doi: 10.1007/s10875-010-9430-5. Epub 2010 Jun 11.

IL-10/TGF-beta-treated dendritic cells, pulsed with insulin, specifically reduce the response to insulin of CD4+ effector/memory T cells from type 1 diabetic individuals.

Author information

1
Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 52662, Israel. qbhonorio@hotmail.com

Abstract

INTRODUCTION:

Diabetogenic autoreactive T cells with effector/memory characteristics are described in type 1 diabetes patients (T1D). Alternatively activated dendritic cells (aaDCs) have been regarded as promising tools for clinical application in autoimmune diseases (ADs), although their ability to induce antigen-specific tolerance in T cells derived from ADs has yet to be determined.

METHODS:

Monocyte-derived dendritic cells (DCs) were produced utilizing GM-CSF and IL-4, and aaDCs by adding IL-10 and TGF-beta (10/TGF-DC) during differentiation. Both cell groups were insulin-loaded, maturated with lipopolysaccharide, and cocultured with autologous effector/memory T cells derived from T1D individuals, in order to evaluate the induction of insulin-specific tolerance.

RESULTS AND DISCUSSION:

In five of eight T1D patients analyzed in vitro, 10/TGF-DC were able to induce insulin-specific tolerance in effector/memory CD4+ T cells (50.4% +/- 13.2 less proliferation), without affecting the proliferative response to an unrelated antigen (candidin). Tolerance induction was dependent on the current activation state of CD4+ T cells in each patient. 10/TGF-DC-stimulated T cells acquired an IL-2(low)IFN-gamma(low)IL-10(high) cytokine profile, and their hyporesponsiveness could be reverted upon exposure to IL-2. This study shows a perspective about the in vitro ability of monocyte-derived 10/TGF-DC to induce antigen-specific tolerance in effector/memory T cells generated during the course of an autoimmune disease.

PMID:
20544263
DOI:
10.1007/s10875-010-9430-5
[Indexed for MEDLINE]
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