Impairment of T-regulatory cells in cord blood of atopic mothers.
BACKGROUND
Maternal atopy is a strong predictor for the development of childhood allergic diseases. The underlying mechanisms are ill defined, yet regulatory T (Treg) and T(H)17 cells may play a key role potentially shaping the early immune system toward a proallergic or antiallergic immune regulation.


OBJECTIVE
We examined T(H)1/T(H)2, Treg, and T(H)17 cell responses to innate (lipid A/peptidoglycan) and mitogen/adaptive (phytohemagglutinin/Dermatophagoides pteronyssinus 1) immune stimulation in cord blood from offspring of atopic/nonatopic mothers.


METHODS
Cord blood mononuclear cells from 161 healthy neonates (59% nonatopic, 41% atopic mothers) were investigated regarding Treg and T(H)17 cells (mRNA/surface markers), suppressive function, and proliferation/cytokine secretion.


RESULTS
Cord blood from offspring of atopic mothers showed fewer innate-induced Treg cells (CD4(+)CD25(+)high), lower mRNA expression of associated markers (glucocorticoid-induced tumor necrosis factor receptor-related protein/lymphocyte activation gene 3; P < .05), and a trend toward lower Forkhead box transcription factor 3 (Foxp3) expression. Treg cell function was impaired in mitogen-induced suppression of T effector cells in cord blood of offspring from atopic mothers (P = .03). Furthermore, IL-10 and IFN-gamma secretion were decreased in innate-stimulated cord blood of offspring from atopic mothers (P = .04/.05). Innate-induced IL-17 was independent of maternal atopy and highly correlated with IL-13 secretion.


CONCLUSIONS
In offspring of atopic mothers, Treg cell numbers, expression, and function were impaired at birth. T(H)17 cells were correlated with T(H)2 cells, independently of maternal atopy.
Department of Pulmonary and Allergy, University Children's Hospital Munich, Munich, Germany. Bianca.Schaub@med.uni-muenchen.de
Bianca
B
Schaub
Jing
J
Liu
Sabine
S
Höppler
Severine
S
Haug
Christine
C
Sattler
Anna
A
Lluis
Sabina
S
Illi
Erika
E
von Mutius
D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis; D060908:CTLA-4 Antigen; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D015870:Gene Expression; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007231:Infant, Newborn / Q000276:immunology*; D008297:Male; D009035:Mothers; D012333:RNA, Messenger / Q000032:analysis; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053450:Glucocorticoid-Induced TNFR-Related Protein; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human; D016212:Transforming Growth Factor beta