Longitudinal relationship of early life immunomodulatory T cell phenotype and function to development of allergic sensitization in an urban cohort
Article first published online: 9 NOV 2011
© 2011 Blackwell Publishing Ltd
Clinical & Experimental Allergy
Volume 42, Issue 3, pages 392–404, March 2012
How to Cite
- Issue published online: 22 FEB 2012
- Article first published online: 9 NOV 2011
- Manuscript Accepted: 24 AUG 2011
- Manuscript Revised: 19 AUG 2011
- Manuscript Received: 17 JAN 2011
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- NO1-AI-25496. Grant Number: NO1-AI-25482
- National Center for Research Resources
- National Institutes of Health. Grant Number: M01 RR00533
- suppressive index;
- T regulatory cells;
Immunomodulatory T cells are thought to influence development of allergy and asthma, but early life longitudinal data on their phenotype and function are lacking.
As part of the Urban Environment and Childhood Asthma (URECA) study, we investigated the development of immunomodulatory T cell phenotype and function, and characterized their relation to allergic disease progression from birth through to 2 years of age.
Immunomodulatory T cell phenotype and function in cord blood mononuclear cells (CBMC) and peripheral blood mononuclear cells (PBMC) at 1 and 2 years of age were characterized by analysing CD25bright and FoxP3+ expression, proliferative responses and cytokine production. The relation of immunomodulatory T cell characteristics to allergic sensitization and disease at 1- and 2-years of age was investigated.
The proportion of CD4+CD25bright and CD4+CD25+FoxP3+ T cells (n = 114, 83, 82 at birth, 1- and 2-years respectively) increased significantly, whereas there were no significant changes in the suppressive function of CD25+ T cells (n = 78, 71, 81 at birth, 1- and 2-years respectively). Birth immunomodulatory T cell characteristics were not related to subsequent allergic sensitization or disease. However, increases in the numbers of CD4+CD25bright cells and their ability to suppress lymphoproliferative responses at 1 year of age were associated with reduced allergic sensitization at 1 (P = 0.03) and 2 (P = 0.02) years of age. Production of the anti-inflammatory cytokine IL-10 by CD25+ T cells appeared to mediate this protective suppressive function. In contrast, by 2 years of age, we observed the emergence of a positive association of CD4+CD25+FoxP3+ T cell numbers with allergic sensitization (P = 0.05) and eczema (P = 0.02).
Conclusions and clinical relevance
These findings suggest that the relationship between immunomodulatory T cell subsets, allergic sensitization and eczema is developmentally regulated. In the first year of life, CD4+CD25+IL-10 producing T cells are associated with a reduced incidence of allergic sensitization. Once allergic sensitization or eczema is established, CD4+CD25+FoxP3+ T-reg cells expand to potentially counteract the allergic inflammatory response. Understanding the relationship between development of immunoregulatory T cells and early onset atopy could lead to new preventive strategies for allergic diseases.