Tolerogenic dendritic cells induce antigen-specific hyporesponsiveness in insulin- and glutamic acid decarboxylase 65-autoreactive T lymphocytes from type 1 diabetic patients.
Clin Immunol
; 154(1): 72-83, 2014 Sep.
Article
em En
| MEDLINE
| ID: mdl-24993292
ABSTRACT
Tolerogenic dendritic cells (tDC) constitute a promising therapy for autoimmune diseases, since they can anergize T lymphocytes recognizing self-antigens. Patients with type 1 diabetes mellitus (T1D) have autoreactive T cells against pancreatic islet antigens (insulin, glutamic acid decarboxylase 65 -GAD65-). We aimed to determine the ability of tDC derived from T1D patients to inactivate their insulin- and GAD65-reactive T cells. CD14+ monocytes and CD4+CD45RA- effector/memory lymphocytes were isolated from 25 patients. Monocyte-derived DC were generated in the absence (control, cDC) or presence of IL-10 and TGF-ß1 (tDC), and loaded with insulin or GAD65. DC were cultured with T lymphocytes (primary culture), and cell proliferation and cytokine secretion were determined. These lymphocytes were rechallenged with insulin-, GAD65- or candidin-pulsed cDC (secondary culture) to assess whether tDC rendered T cells hyporesponsive to further stimulation. In the primary cultures, tDC induced significant lower lymphocyte proliferation and IL-2 and IFN-γ secretion than cDC; in contrast, tDC induced higher IL-10 production. Lymphocytes from 60% of patients proliferated specifically against insulin or GAD65 (group 1), whereas 40% did not (group 2). Most patients from group 1 had controlled glycemia. The secondary cultures showed tolerance induction to insulin or GAD65 in 14 and 10 patients, respectively. A high percentage of these patients (70-80%) belonged to group 1. Importantly, tDC induced antigen-specific T-cell hyporesponsiveness, since the responses against unrelated antigens were unaffected. These results suggest that tDC therapy against multiple antigens might be useful in a subset of T1D patients.
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Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Células Dendríticas
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Linfócitos T
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Diabetes Mellitus Tipo 1
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Glutamato Descarboxilase
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Insulina
Limite:
Adolescent
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Adult
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Child
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article