Association of T-cell reactivity with beta-cell function in recent onset type 1 diabetes patients.
OBJECTIVE
The aim of the current study was to investigate whether autoantigen directed T-cell reactivity relates to beta-cell function during the first 78 weeks after diagnosis of type 1 diabetes.


METHODS
50 adults and 49 children (mean age 27.3 and 10.9 years respectively) with recent onset type 1 diabetes who participated in a placebo-controlled trial of immune intervention with DiaPep277 were analyzed. Secretion of interferon (IFN)-gamma, interleukin (IL)-5, IL-13 and IL-10 by single peripheral mononuclear cells (PBMC) upon stimulation with islet antigens GAD65, heat shock protein 60 (Hsp60) protein-tyrosine-phosphatase-like-antigen (pIA2) or tetanus toxoid (TT) was determined applying ELISPOT; beta-cell function was evaluated by glucagon stimulated C-peptide. Multivariate regression analysis was applied.


RESULTS
In general, number of islet antigen-reactive cells decreased over 78 weeks in both adults and children, whereas reactivity to TT was not reduced. In addition, there was an association between the quality of immune cell responses and beta-cell function. Overall, increased responses by IFN-gamma secreting cells were associated with lower beta-cell function whereas IL-5, IL-13 and IL-10 cytokine responses were positively associated with beta-cell function in adults and children. Essentially, the same results were obtained with three different models of regression analysis.


CONCLUSIONS
The number of detectable islet-reactive immune cells decreases within 1-2 years after diagnosis of type 1 diabetes. Cytokine production by antigen-specific PBMC reactivity is related to beta-cell function as measured by stimulated C-peptide. Cellular immunity appears to regress soon after disease diagnosis and begin of insulin therapy.
Pfleger
Christian
C
Institute of Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich-Heine-University Duesseldorf, Auf'm Hennekamp 65, 40225 Duesseldorf, Germany. ch.pfleger@web.de
Meierhoff
Guido
G
Kolb
Hubert
H
Schloot
Nanette C
NC
D000293:Adolescent; D000328:Adult; D001324:Autoantigens / Q000276:immunology*; D002096:C-Peptide / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism*; D008297:Male; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D001324:Autoantigens; D002096:C-Peptide; D016207:Cytokines; D005934:Glucagon