Adult-onset type 1 diabetes patients display decreased IGRP-specific Tr1 cells in blood.
The breakdown of immune tolerance against islet antigens causes type 1 diabetes (T1D). The antigens associated with adult-onset T1D (AT1D) remain largely undefined. It is possible that AT1D patients display a unique type of CD4(+) T cells specific for a certain islet antigen. Here we analyzed the cytokine production profiles of CD4(+) helper T (Th) cells that are specific for three islet antigens; GAD65, preproinsulin, and IGRP in patients with AT1D, juvenile-onset T1D (JT1D), and age-, gender- and human leukocyte antigen (HLA)-matched control adults. While IGRP-specific Th cells in AT1D patients were dominantly Th1 cells, IGRP-specific Th cells in control adults and JT1D patients were dominantly Th2 and T regulatory type 1 (Tr1) cells. Notably, the frequency of IGRP-specific Tr1 cells was significantly lower in AT1D patients than in control adults and JT1D patients. In conclusion, our study suggests that IGRP-specific Th cells play a unique pathogenic role in AT1D.
Baylor Institute for Immunology Research, Dallas, TX, USA; National Center for Global Health and Medicine, Tokyo, Japan.
Daisuke
D
Chujo
Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
Thien-Son
TS
Nguyen
Baylor Institute for Immunology Research, Dallas, TX, USA.
Emile
E
Foucat
Baylor Institute for Immunology Research, Dallas, TX, USA.
Derek
D
Blankenship
Baylor Institute for Immunology Research, Dallas, TX, USA.
Jacques
J
Banchereau
Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
Gerald T
GT
Nepom
Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
Damien
D
Chaussabel
Baylor Institute for Immunology Research, Dallas, TX, USA. Electronic address: HidekiU@baylorhealth.edu.
Hideki
H
Ueno
D000328:Adult; D017668:Age of Onset; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D005260:Female; D005952:Glucose-6-Phosphatase / Q000276:immunology* / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000276:immunology / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D007328:Insulin; D011498:Protein Precursors; C013737:preproinsulin; D005952:Glucose-6-Phosphatase; C492194:G6PC2 protein, human; C505804:GAD55, human; D005968:Glutamate Decarboxylase
CD4 T cells; Islet antigens; Islet-specific glucose 6 phosphatase catalytic subunit-related protein; T regulatory type 1 (Tr1) cells; Type 1 diabetes