Reduced IL-2-induced IL-12 responsiveness in atopic children.
Atopy may be associated with a reduced T-cell function particularly regarding maturation of T helper 1 (Th1) responses. We hypothesized that atopic children may have a reduced capacity to up-regulate the beta2 subunit of the interleukin-12 (IL-12) receptor (IL-12Rbeta2, the signal-transducing component). The study included 38 children followed from birth to the age of 7 years. Twenty one had a cumulative history of atopic disease, whereas 17 had none. Sixteen out of 21 children also had atopic symptoms within the past year (current), out of whom 10 children had atopic airway symptoms. The expression of IL-12Rbeta2 mRNA was analyzed by quantitative real-time PCR and the secretion of interferon-gamma (IFN-gamma), IL-5 and IL-10 was assessed by enzyme-linked immunosorbent assay (ELISA). Children with current atopic airway symptoms and high levels of total IgE up-regulated IL-12Rbeta2 mRNA expression less than non-atopic children with low IgE levels after IL-2 stimulation. This was accompanied by a low IL-2- and IL-12-induced IFN-gamma production, possibly reflecting the reduced capacity of atopic children to up-regulate the IL-12 receptor. As IL-2 is needed to initiate and sustain immune responses and IL-12 promotes Th1 responses, this may contribute to the Th2-skewed pattern in atopic children.
Aniansson Zdolsek
Helena
H
Department of Molecular and Clinical Medicine, Division of Paediatrics and Clinical Research Center, Faculty of Health Sciences, Linköping University, Sweden. helzd@imk.liu.se
Janefjord
Camilla K
CK
Fälth-Magnusson
Karin
K
Jenmalm
Maria C
MC
D015415:Biomarkers / Q000097:blood; D002648:Child; D002669:Child Welfare; D016207:Cytokines / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D005500:Follow-Up Studies; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000378:metabolism*; D007073:Immunoglobulin E / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000008:administration & dosage / Q000378:metabolism*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000378:metabolism*; D015848:Interleukin-5 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000378:metabolism; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000096:biosynthesis; D053707:Receptors, Interleukin-12; D012882:Skin Tests; D013223:Statistics as Topic; D013548:Sweden; D015854:Up-Regulation / Q000502:physiology
D015415:Biomarkers; D016207:Cytokines; C508439:IL12RB2 protein, human; D007376:Interleukin-2; D015848:Interleukin-5; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D016753:Interleukin-10; D018664:Interleukin-12; D007073:Immunoglobulin E; D007371:Interferon-gamma