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Activation of Islet Autoreactive Naïve T Cells in Infants Is Influenced by Homeostatic Mechanisms and Antigen-Presenting Capacity

Islet autoimmunity precedes type 1 diabetes onset. We previously found that islet autoimmunity rarely starts before 6 months of age but reaches its highest incidence already at ∼1 year of age. We now examine whether homeostatic expansion and immune competence changes seen in a maturating immune syst...

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Autores principales: Heninger, Anne-Kristin, Monti, Paolo, Wilhelm, Carmen, Schwaiger, Petra, Kuehn, Denise, Ziegler, Anette-G., Bonifacio, Ezio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661654/
https://www.ncbi.nlm.nih.gov/pubmed/23349478
http://dx.doi.org/10.2337/db12-0942
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author Heninger, Anne-Kristin
Monti, Paolo
Wilhelm, Carmen
Schwaiger, Petra
Kuehn, Denise
Ziegler, Anette-G.
Bonifacio, Ezio
author_facet Heninger, Anne-Kristin
Monti, Paolo
Wilhelm, Carmen
Schwaiger, Petra
Kuehn, Denise
Ziegler, Anette-G.
Bonifacio, Ezio
author_sort Heninger, Anne-Kristin
collection PubMed
description Islet autoimmunity precedes type 1 diabetes onset. We previously found that islet autoimmunity rarely starts before 6 months of age but reaches its highest incidence already at ∼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 (CB) 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 CB 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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spelling pubmed-36616542014-06-01 Activation of Islet Autoreactive Naïve T Cells in Infants Is Influenced by Homeostatic Mechanisms and Antigen-Presenting Capacity Heninger, Anne-Kristin Monti, Paolo Wilhelm, Carmen Schwaiger, Petra Kuehn, Denise Ziegler, Anette-G. Bonifacio, Ezio Diabetes Original Research Islet autoimmunity precedes type 1 diabetes onset. We previously found that islet autoimmunity rarely starts before 6 months of age but reaches its highest incidence already at ∼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 (CB) 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 CB 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. American Diabetes Association 2013-06 2013-05-17 /pmc/articles/PMC3661654/ /pubmed/23349478 http://dx.doi.org/10.2337/db12-0942 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Research
Heninger, Anne-Kristin
Monti, Paolo
Wilhelm, Carmen
Schwaiger, Petra
Kuehn, Denise
Ziegler, Anette-G.
Bonifacio, Ezio
Activation of Islet Autoreactive Naïve T Cells in Infants Is Influenced by Homeostatic Mechanisms and Antigen-Presenting Capacity
title Activation of Islet Autoreactive Naïve T Cells in Infants Is Influenced by Homeostatic Mechanisms and Antigen-Presenting Capacity
title_full Activation of Islet Autoreactive Naïve T Cells in Infants Is Influenced by Homeostatic Mechanisms and Antigen-Presenting Capacity
title_fullStr Activation of Islet Autoreactive Naïve T Cells in Infants Is Influenced by Homeostatic Mechanisms and Antigen-Presenting Capacity
title_full_unstemmed Activation of Islet Autoreactive Naïve T Cells in Infants Is Influenced by Homeostatic Mechanisms and Antigen-Presenting Capacity
title_short Activation of Islet Autoreactive Naïve T Cells in Infants Is Influenced by Homeostatic Mechanisms and Antigen-Presenting Capacity
title_sort activation of islet autoreactive naïve t cells in infants is influenced by homeostatic mechanisms and antigen-presenting capacity
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661654/
https://www.ncbi.nlm.nih.gov/pubmed/23349478
http://dx.doi.org/10.2337/db12-0942
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