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.
BACKGROUND
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.


CONCLUSIONS
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.
Torres-Aguilar
Honorio
H
Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 52662, Israel. qbhonorio@hotmail.com
Sánchez-Torres
Carmen
C
Jara
Luis J
LJ
Blank
Miri
M
Shoenfeld
Yehuda
Y
D000328:Adult; D017951:Antigen Presentation / Q000187:drug effects; D000943:Antigens, Differentiation / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000628:therapy*; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007156:Immunologic Memory; D007167:Immunotherapy; D007328:Insulin / Q000378:metabolism; D016753:Interleukin-10 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D000943:Antigens, Differentiation; D007328:Insulin; D016212:Transforming Growth Factor beta; D016753:Interleukin-10