Th2 Dominance of T Helper Cell Response to Preproinsulin in Individuals with Preclinical Type 1 Diabetes

Th2 Dominance of T Helper Cell Response to Preproinsulin in Individuals with Preclinical Type 1 Diabetes

: In human type 1 diabetes (T1D) autoantibodies to insulin precede clinical disease, while little is known about the contribution of insulin‐specific T lymphocytes—in particular, T helper (Th) subsets. Here we have studied the in vivo primed cytokine response to preproinsulin in peripheral blood mon...

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Bibliographic Details
Published in:Annals of the New York Academy of Sciences Vol. 958; no. 1; pp. 209 - 213
Main Authors: DURINOVIC-BELLÓ, IVANA, RIEDL, MARTINA, ROSINGER, SILKE, MAISEL, NICOLA, KALBACHER, HUBERT, DEEG, MARTIN, SCHRECKLING, HANS-JÜRGEN, SCHLOSSER, MICHAEL, ZIEGLER, MANFRED, KUEHNL, PETER, BOEHM, BERNHARD O.
Format: Journal Article
Language:English
Published: Oxford, UK Blackwell Publishing Ltd 01-04-2002
Subjects:
Adolescent
Adult
CD45RO+ memory and CD45RA+ naive/resting Th cells
Cells, Cultured
Child
Child, Preschool
cytokines
Diabetes Mellitus, Type 1 - immunology
Female
HLA Antigens - immunology
Humans
Immunologic Memory - immunology
Insulin
Interleukin-4 - metabolism
Interleukin-5 - metabolism
Leukocyte Common Antigens - metabolism
Male
Middle Aged
PBMC
preproinsulin
Proinsulin - pharmacology
Protein Precursors - pharmacology
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Th2 Cells - drug effects
Th2 Cells - immunology
Th2 Cells - metabolism
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Summary:: In human type 1 diabetes (T1D) autoantibodies to insulin precede clinical disease, while little is known about the contribution of insulin‐specific T lymphocytes—in particular, T helper (Th) subsets. Here we have studied the in vivo primed cytokine response to preproinsulin in peripheral blood mononuclear cells (PBMCs) and two major Th cell subsets—CD45RO+ memory cells and CD45RA+ naive/resting cells—in 35 individuals with HLA‐DRB1*04, DQB1*0302 diabetes risk marker: 12 patients with T1D, 12 autoantibody‐positive (Ab+) individuals, and 11 healthy controls. Cytokine secretion (TNF‐α, IFN‐γ, IL‐2, IL‐4, IL‐5, and IL‐10) was measured in the supernatants of the cultures stimulated with 21 overlapping preproinsulin peptides as well as proinsulin and insulin. In Ab+ individuals our results reveal higher IL‐4 levels in CD45RO+ memory cells and higher IL‐5 levels in CD45RA+ naive/resting cells, while higher IL‐2 production was found in PBMCs. In contrast, in PBMCs of T1D patients higher IFN‐γ and IL‐10 secretion was found. Our data delineate characteristic cytokine patterns in peripheral T lymphocytes from patients at different stages of the T1D development.
Bibliography:istex:14D212AD8F0929D37192FA1A72DCF3C735D8F74C
ark:/67375/WNG-115P0SX8-V
ArticleID:NYAS209
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0077-8923
1749-6632
DOI:10.1111/j.1749-6632.2002.tb02971.x