IFN-gamma and IL-10 islet-antigen-specific T cell responses in autoantibody-negative first-degree relatives of patients with type 1 diabetes

L G Petrich de Marquesini, J Fu, K J Connor, A J Bishop, N E McLintock, C Pope, F S Wong, C M Dayan, Caroline Pope

Research output: Contribution to journalArticle (Academic Journal)peer-review

39 Citations (Scopus)

Abstract

AIMS/HYPOTHESIS: Islet antibody-negative first-degree relatives of type 1 diabetes patients have a very low risk of developing diabetes. We studied the balance between IFN-gamma (proinflammatory) and IL-10 (regulatory) T cell responses in these participants.

METHODS: Peripheral blood T cells from adult (18-50 years old, n = 40) DRB1*0401-positive first-degree relatives negative for GAD and tyrosine phosphatase-like insulinoma antigen 2 (IA-2) antibodies were tested for IFN-gamma and IL-10 responses in a sensitive cytokine enzyme-linked immunospot assay against a panel of seven peptide epitopes derived from IA-2 and proinsulin. Comparison was made with HLA-matched newly diagnosed type 1 diabetic patients (n = 42) and healthy controls (n = 39).

RESULTS: First-degree relatives and newly diagnosed type 1 diabetic patients displayed a similar frequency of IFN-gamma responses to the peptide panel and both were significantly greater than in healthy controls (relatives 9.6%, patients 11.8%, controls 4.0%, p = 0.003). First-degree relatives and newly diagnosed type 1 diabetic patients also showed similar frequencies of IL-10 responses, which were significantly lower than in healthy controls (relatives 7.1%, patients 9.0%, controls 15.8%, p = 0.003). However, individual IL-10 responses of first-degree relatives were similar in size to those in healthy controls and larger than those in newly diagnosed type 1 diabetic patients (relatives median 29 spot-forming cells/1 x 10(6) peripheral blood mononuclear cells, controls 33, patients 11, p = 0.02).

CONCLUSIONS/INTERPRETATION: Taken together, these results suggest that antibody-negative first-degree relatives have a balance of proinflammatory and regulatory T cells, which is intermediate between that of newly diagnosed type 1 diabetic patients and healthy controls. This suggests that even a moderate regulatory response may be sufficient to prevent the development of clinical type 1 diabetes in genetically predisposed individuals.

Original languageEnglish
Pages (from-to)1451-60
Number of pages10
JournalDiabetologia
Volume53
Issue number7
DOIs
Publication statusPublished - Jul 2010

Keywords

  • Adolescent
  • Adult
  • Autoantibodies
  • Diabetes Mellitus, Type 1
  • Family
  • Female
  • Humans
  • Interferon-gamma
  • Interleukin-10
  • Male
  • Middle Aged
  • T-Lymphocytes
  • Young Adult

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