IFN-gamma and IL-10 islet-antigen-specific T cell responses in autoantibody-negative first-degree relatives of patients with type 1 diabetes.
OBJECTIVE
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
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.
Petrich de Marquesini
L G
LG
Henry Wellcome Laboratory for Integrative Neuroscience and Endocrinology, Dorothy Hodgkin Building, Clinical Science at South Bristol, University of Bristol, Whitson St, Bristol, BS1 3NY, UK.
Fu
J
J
Connor
K J
KJ
Bishop
A J
AJ
McLintock
N E
NE
Pope
C
C
Wong
F S
FS
Dayan
C M
CM
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005190:Family; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
D001323:Autoantibodies; D016753:Interleukin-10; D007371:Interferon-gamma