Document Detail

Cytokine production by cord blood mononuclear cells stimulated with cows milk proteins in vitro: interleukin-4 and transforming growth factor beta-secreting cells detected in the CD45RO T cell population in children of atopic mothers.
MedLine Citation:
PMID:  12752590     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Food antigens from the maternal circulation may sensitize fetal T cells in utero and be an important determinant in the development of food allergy. METHODS: Here we have examined the spontaneous and recall response to cow's milk proteins of cord blood mononuclear cells (CBMC) of newborn children, using single cell ELISPOT assays. RESULTS: In term newborns, confirming previous studies, the spontaneous cytokine response of CBMC is dominated by IL-4, IL-5, IL-10, and as shown here for the first time, TGF-beta. For TGF-beta only, the response of samples from infants of atopic mothers was significantly lower than samples from infants of non-atopic mothers. In vitro stimulation of CBMC with bovine serum albumin, casein and beta-lactoglobulin resulted in a significant increase of all cytokine-secreting cells, again dominated by T helper type 2 (Th2) cytokines. There was a clear tendency for samples from infants of atopic mothers to have lower Th2 responses than samples from infants of non-atopic mothers, which was particularly significant for both IL-4 and TGF-beta. Spontaneous cytokine secreting cells were virtually absent in cord blood from infants < 34 weeks gestation, as were cows milk protein-induced responses, although they were readily detectable in samples from infants aged > 34 weeks. To explore whether the cytokine secreting cells were in the naive CD4+ CD45RA population or memory CD4+ CD45RO T cells, these subsets were purified by positive and negative selection and tested for spontaneous and cows milk protein-induced cytokine responses. Strikingly, although the responses were small, the CD45RO+ cells from children of atopic mothers showed significant spontaneous and antigen-specific IL-4 and TGF-beta responses, whereas the same population from infants of non-atopic mothers showed virtually no response. In addition CD45RA+ cells from infants of mothers with maternal atopy showed decreased IL-4 and TGF-beta responses, especially the latter. CONCLUSIONS: The cows milk antigen-specific IL-4 and TGF-beta responses preferentially seen in the memory cell subset of infants with a maternal history of atopy strongly suggests Th2 skewing to dietary antigens in utero.
A C Hauer; M Riederer; A Griessl; H Rosegger; T T MacDonald
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology     Volume:  33     ISSN:  0954-7894     ISO Abbreviation:  Clin. Exp. Allergy     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-05-19     Completed Date:  2003-09-04     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8906443     Medline TA:  Clin Exp Allergy     Country:  England    
Other Details:
Languages:  eng     Pagination:  615-23     Citation Subset:  IM    
Universitätsklinik fur Kinder- und Jugendheilkunde, Karl-Franzens-Universität, Graz, Austria.
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MeSH Terms
Antigens, CD45 / analysis
CD4-Positive T-Lymphocytes / immunology
Cells, Cultured
Cytokines / biosynthesis*
Fetal Blood / immunology*
Hypersensitivity, Immediate / immunology*
Infant, Newborn
Infant, Premature / immunology
Interleukin-4 / biosynthesis
Maternal-Fetal Exchange / immunology
Milk Proteins / immunology*
Pregnancy Complications / immunology
T-Lymphocyte Subsets / immunology*
Transforming Growth Factor beta / biosynthesis
Reg. No./Substance:
0/Cytokines; 0/Milk Proteins; 0/Transforming Growth Factor beta; 207137-56-2/Interleukin-4; EC, CD45

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