Both authors contributed equally to the manuscript.
Impairment of T helper and T regulatory cell responses at birth
Article first published online: 10 OCT 2008
© 2008 The Authors. Journal compilation © 2008 Blackwell Munksgaard
Volume 63, Issue 11, pages 1438–1447, November 2008
How to Cite
Schaub, B., Liu, J., Schleich, I., Höppler, S., Sattler, C. and Von Mutius, E. (2008), Impairment of T helper and T regulatory cell responses at birth. Allergy, 63: 1438–1447. doi: 10.1111/j.1398-9995.2008.01685.x
- Issue published online: 10 OCT 2008
- Article first published online: 10 OCT 2008
- Accepted for publication 27 January 2008
- T helper type 17/T-regulatory cells;
- toll-like receptors
Background: There is strong evidence that reduced exposures to microbial compounds triggering innate immune responses early in life are critical for the development of allergic illnesses. The underlying mechanisms remain unknown, but will include T-cell responses either along T helper type 1 (Th1)/Th2 pathways or via T regulatory and Th17 cells. Yet, little is known about innate immune responses and the function of T regulatory/Th17 cells at birth. The aim of this study was to investigate T-cell responses to innate (Lipid A/LpA, peptidoglycan/Ppg) and adaptive (phytohemagglutinin) stimuli at birth and to compare these findings with adult immune responses.
Methods: Cord and peripheral blood mononuclear cells including T regulatory and Th17 cells from 25 neonates and 25 adults were examined for proliferation, cytokine secretion, surface, mRNA expression and functional suppression assays.
Results: Proliferation and cytokine responses to innate stimuli were less mature at birth than in adulthood. T regulatory and Th17 cells were less expressed in cord than in adult blood (Ppg-induced Foxp3, P = 0.001, LpA-induced CD4+ CD25+ high, P = 0.02; Th17 : P < 0.0001). Mitogen-induced suppression of T-regulatory cells on T-effector cell function was less efficient in cord than in adult blood (P = 0.01). At both ages, Th17 cells were correlated with Th1/Th2 cells (P < 0.01), but not with interleukin-10 secretion following innate-stimulation.
Conclusion: Innate immune responses are immature at birth. Furthermore, the function of T regulatory and Th17 cells is impaired. Th17 cells in association with Th1/Th2 cells may be involved in early immuno-modulation. Potent innate immune stimulation early in life can potentially contribute to protection from allergic diseases.