Regulatory cells, cytokine pattern and clinical risk factors for asthma in infants and young children with recurrent wheeze.
BACKGROUND
Several risk factors for asthma have been identified in infants and young children with recurrent wheeze. However, published literature has reported contradictory findings regarding the underlying immunological mechanisms.


OBJECTIVE
This study was designed to assess and compare the immunological status during the first 2 years in steroid-naive young children with >or= three episodes of physician-confirmed wheeze (n=50), with and without clinical risk factors for developing subsequent asthma (i.e. parental asthma or a personal history of eczema and/or two of the following: wheezing without colds, a personal history of allergic rhinitis and peripheral blood eosinophilia >4%), with age-matched healthy controls (n=30).


METHODS
Peripheral blood CD4(+)CD25(+) and CD4(+)CD25(high) T cells and their cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), GITR and Foxp3 expression were analysed by flow cytometry. Cytokine (IFN-gamma, TGF-beta and IL-10), CTLA-4 and Foxp3 mRNA expression were evaluated (real-time PCR) after peripheral blood mononuclear cell stimulation with phorbol 12-myristate 13-acetate (PMA) (24 h) and house dust mite (HDM) extracts (7th day).


RESULTS
Flow cytometry results showed a significant reduction in the absolute number of CD4(+)CD25(high) and the absolute and percentage numbers of CD4(+)CD25(+)CTLA-4(+) in wheezy children compared with healthy controls. Wheezy children at a high risk of developing asthma had a significantly lower absolute number of CD4(+)CD25(+) (P=0.01) and CD4(+)CD25(high) (P=0.04), compared with those at a low risk. After PMA stimulation, CTLA-4 (P=0.03) and Foxp3 (P=0.02) expression was diminished in wheezy children compared with the healthy children. After HDM stimulation, CTLA-4 (P=0.03) and IFN-gamma (P=0.04) expression was diminished in wheezy children compared with healthy children. High-risk children had lower expression of IFN-gamma (P=0.03) compared with low-risk and healthy children and lower expression of CTLA-4 (P=0.01) compared with healthy children.


CONCLUSIONS
Although our findings suggest that some immunological parameters are impaired in children with recurrent wheeze, particularly with a high risk for asthma, further studies are needed in order to assess their potential as surrogate predictor factors for asthma in early life.
Serviço de Imunoalergologia, Centro Hospitalar Lisboa Central, Rua Jacinta Marto, Lisboa, Portugal. miguel.borrego@sapo.pt
L M
LM
Borrego
M J
MJ
Arroz
P
P
Videira
C
C
Martins
H
H
Guimarães
G
G
Nunes
A L
AL
Papoila
H
H
Trindade
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D039741:Antigens, Dermatophagoides / Q000276:immunology; D001249:Asthma / Q000276:immunology*; D060908:CTLA-4 Antigen; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D012135:Respiratory Sounds / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015703:Antigens, CD; D039741:Antigens, Dermatophagoides; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; D012333:RNA, Messenger; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate