GAD-alum treatment induces GAD65-specific CD4+CD25highFOXP3+ cells in type 1 diabetic patients.
Type 1 diabetes results from autoimmune destruction of insulin producing pancreatic β-cells. We have shown that treatment with alum-formulated glutamic acid decarboxylase 65 (GAD-alum) preserved residual insulin secretion and induced antigen-specific responses in children with recent onset type 1 diabetes. The aim of this study was to further investigate the immunomodulatory effect of GAD-alum, focusing on CD4(+)CD25(high) cells and their association to cytokine secretion. Samples obtained 21 and 30months after the initial injection of GAD-alum or placebo were included in the present study. GAD(65)-stimulation enhanced the percentage of CD4(+)CD25(high)FOXP3(+) cells, but reduced the percentage of CD4(+)CD25(+) cells, in samples from the GAD-alum treated group. Further, the GAD(65)-induced secretion of IL-5, -10, and -13 correlated with the expression of CD4(+)CD25(high)FOXP3(+) cells, but inversely with CD4(+)CD25(+) cells. These new data suggest that GAD-alum treatment induced GAD(65)-specific T cells with regulatory features.
Division of Pediatrics & Diabetes Research Center, Department of Clinical & Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden. maria.hjorth@liu.se
Maria
M
Hjorth
Stina
S
Axelsson
Anna
A
Rydén
Maria
M
Faresjö
Johnny
J
Ludvigsson
Rosaura
R
Casas
D000293:Adolescent; D000534:Alum Compounds / Q000008:administration & dosage; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002452:Cell Count; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000276:immunology / Q000628:therapy*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D005968:Glutamate Decarboxylase / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000534:Alum Compounds; D001323:Autoantibodies; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D007378:Interleukins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C041524:aluminum sulfate; D007371:Interferon-gamma; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2