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Heninger, A.K.* ; Monti, P.* ; Wilhelm, C.* ; Schwaiger, P.* ; Kuehn, D.* ; Ziegler, A.-G. ; Bonifacio, E.*

Activation of islet autoreactive naive T cells in infants is influenced by homeostatic mechanisms and antigen presenting capacity.

Diabetes 62, 2059-2066 (2013)

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Open Access Green as soon as Postprint is submitted to ZB.

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Islet autoimmunity precedes type 1 diabetes onset. We previously found that islet autoimmunity rarely starts before age six months but reaches its highest incidence already at around 1 year of age. We now examine whether homeostatic expansion and immune competence changes seen in a maturating immune system may account for this marked variation in islet autoimmunity risk in the first year of life. We found naïve proinsulin- and GAD65-responsive T cells in cord blood of healthy newborns, with highest responses observed in children with type 1 diabetes susceptible HLA-DRB1/DQB1 genotypes. Homeostatic expansion characteristics with increased IL-7 concentrations and enhanced T cell responsiveness to IL-7 were observed throughout the first year of life. However, the ability of antigen-presenting cells to activate naïve T cells was compromised at birth, and cord blood monocytes had low surface expression of CD40 and HLA class II. In contrast, antigen presentation and expression of these molecules had reached competent adult levels by the high incidence age of 8 months. We propose that temporal changes in islet autoimmunity seroconversion in infants are a consequence of the changing balance between homeostatic drive and antigen presentation competence. These findings are relevant for early prevention of type 1 diabetes.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Hematopoietic Stem-cells ; Human Thymus ; Peripheral-blood ; Immune-responses ; Insulin Gene ; Il-7 ; Autoimmunity ; Expression ; Newborns ; Fetal

ISSN (print) / ISBN 0012-1797

e-ISSN 1939-327X

Journal Diabetes

Quellenangaben Volume: 62, Issue: 6, Pages: 2059-2066

Publisher American Diabetes Association

Publishing Place Alexandria, VA.

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes Research (IDF)
Institute of Pancreatic Islet Research (IPI)