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

Petrich de Marquesini, L. G., Fu, J., Connor, K. J., Bishop, Amanda J., McLintock, N. E., Pope, Charles A., Wong, Florence Susan ORCID: https://orcid.org/0000-0002-2812-8845 and Dayan, Colin Mark ORCID: https://orcid.org/0000-0002-6557-3462 2010. IFN-γ and IL-10 islet-antigen-specific T cell responses in autoantibody-negative first-degree relatives of patients with type 1 diabetes. Diabetologia 53 (7) , pp. 1451-1460. 10.1007/s00125-010-1739-3

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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-γ (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-γ 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-γ 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 × 106 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General) R Medicine > RC Internal medicine
Uncontrolled Keywords:	ELISPOT; First-degree relatives; Interferon-gamma; Interleukin-10; Proinsulin; Regulatory T cells; T cells; Type 1 diabetes
Publisher:	Springer
ISSN:	0012-186X
Last Modified:	19 Oct 2022 10:02
URI:	https://orca.cardiff.ac.uk/id/eprint/23024

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