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 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-alpha, IFN-gamma, 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-gamma 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.
Durinovic-Belló
Ivana
I
Department of Internal Medicine I, University of Ulm, Ulm, Germany. ivana.durinovic-bello@medizin.uni-ulm.de
Riedl
Martina
M
Rosinger
Silke
S
Maisel
Nicola
N
Kalbacher
Hubert
H
Deeg
Martin
M
Schreckling
Hans-Jürgen
HJ
Schlosser
Michael
M
Ziegler
Manfred
M
Kuehnl
Peter
P
Boehm
Bernhard O
BO
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007328:Insulin; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011384:Proinsulin / Q000494:pharmacology*; D011498:Protein Precursors / Q000494:pharmacology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism
D006680:HLA Antigens; D007328:Insulin; D015848:Interleukin-5; D011498:Protein Precursors; D015847:Interleukin-4; C013737:preproinsulin; D011384:Proinsulin; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1