Genome-wide association study of vitamin D levels in children: replication in the Western Australian Pregnancy Cohort (Raine) study.

This genome-wide association study (GWAS) utilises data from the Western Australian Pregnancy Cohort (Raine) Study for 25-hydroxyvitamin D (25(OH)D) levels measured in blood collected at age 6 years (n=673) and at age 14 years (n=1140). Replication of significantly associated genes from previous GWASs was found for both ages. Genome-wide significant associations were found both at age 6 and 14 with single nucleotide polymorphisms (SNPs) on chromosome 11p15 in PDE3B/CYP2R1 (age 6: rs1007392, P=3.9 × 10(-8); age14: rs11023332, P=2.2 × 10(-10)) and on chromosome 4q13 in GC (age 6: rs17467825, P=4.2 × 10(-9); age14: rs1155563; P=3.9 × 10(-9)). In addition, a novel association was observed at age 6 with SNPs on chromosome 7p15 near NPY (age 6: rs156299, P=1.3 × 10(-6)) that could be of functional interest in highlighting alternative pathways for vitamin D metabolism in this age group and merits further analysis in other cohort studies.

Fish oil supplementation in early infancy modulates developing infant immune responses.

BACKGROUND: Maternal fish oil supplementation during pregnancy has been associated with altered infant immune responses and a reduced risk of infant sensitization and eczema. OBJECTIVE: To examine the effect of early postnatal fish oil supplementation on infant cellular immune function at 6 months of age in the context of allergic disease. METHODS: In a double-blind randomized controlled trial (ACTRN12606000281594), 420 infants of high atopic risk received fish oil [containing 280 mg docosahexaenoic acid (DHA) and 110 mg eicosapentanoic acid (EPA)] or control oil daily from birth to 6 months. One hundred and twenty infants had blood collected at 6 months of age. Fatty acid levels, induced cytokine responses, T cell subsets and monocyte HLA-DR expression were assessed at 6 months of age. Infant allergies were assessed at 6 and 12 months of age. RESULTS: DHA and EPA levels were significantly higher in the fish oil group and erythrocyte arachidonic acid (AA) levels were lower (all P < 0.05). Infants in the fish oil group had significantly lower IL-13 responses (P = 0.036) to house dust mite (HDM) and higher IFNγ (P = 0.035) and TNF (P = 0.017) responses to phytohaemaglutinin (PHA). Infants with relatively high DHA levels had lower Th2 responses to allergens including lower IL-13 to ß-lactoglobulin (BLG) (P = 0.020), and lower IL-5 to BLG (P = 0.045). CONCLUSIONS AND CLINICAL RELEVANCE: Postnatal fish oil supplementation increased infant n-3 polyunsaturated fatty acid (PUFA) levels and associated with lowered allergen-specific Th2 responses and elevated polyclonal Th1 responses. Our results add to existing evidence of n-3 PUFA having immunomodulatory properties that are potentially allergy-protective.

Vitamin D and atopy and asthma phenotypes in children: a longitudinal cohort study.

Vitamin D has been linked in some studies with atopy- and asthma-associated phenotypes in children with established disease, but its role in disease inception at the community level is less clear. The aim of the present study was to investigate associations between vitamin D status and biological signatures indicative of allergy and asthma development in children aged 6 and 14 years in Perth, WA, Australia (latitude 32° S). Serum vitamin D was assayed in 989 6-yr-olds and 1,380 14-yr-olds from an unselected community birth cohort; 689 subjects were assessed at both ages. Vitamin D levels were assessed as a risk modifier for respiratory and allergic outcomes at both ages, using previously ascertained phenotypic data. The predictive value of vitamin D levels at age 6 yrs for development of clinical phenotypes at age 14 yrs was also examined. Serum vitamin D levels in children of both ages were negatively associated with concurrent allergic phenotypes; sex stratification revealed that this association was restricted mainly to males. Furthermore, vitamin D levels at age 6 yrs were significant predictors of subsequent atopy/asthma-associated phenotypes at age 14 yrs. In an unselected community setting, children (particularly males) with inadequate vitamin D are at increased risk of developing atopy, and subsequently bronchial hyperresponsiveness (BHR) and asthma. In a large unselected cohort, males with inadequate vitamin D at 6 and 14 yrs of age had increased atopy and BHR. Low vitamin D at age 6 yrs was a predictor of atopy and asthma at 14 yrs of age.

Th2-associated immunity to bacteria in teenagers and susceptibility to asthma.

Bacterial colonisation of the airways is associated with increased risk of childhood asthma. Immunoglobulin (Ig)E against bacterial antigens has been reported in some asthmatics, suggesting a role for bacterial-specific type-2 immunity in disease pathogenesis. We aimed to investigate relationships between bacterial-specific IgE amongst teenagers and asthma susceptibility. We measured titres of IgE against Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus in 1,380 teenagers, and related these to asthma symptomatology and immunophenotypes. IgE titres against S. aureus-derived enterotoxins were highest amongst atopics and were associated with asthma risk. Surprisingly, IgE titres against H. influenzae and S. pneumoniae surface antigens were higher, not stratified by atopy and independently associated with decreased asthma risk. The positive association between type-2 immunity to S. aureus and asthma phenotypes probably reflects IgE-mediated effector cell activation via enterotoxin super antigens which are secreted in soluble form. The contrasting benign nature of type-2 immunity to H. influenzae and S. pneumoniae antigens may reflect their lower availability in soluble forms that can crosslink IgE receptors. We theorise that instead they may be processed by antigen presenting cells and presented to type-2 memory cells leading to mucosal secretion of interleukin (IL)-4/IL-13, a mechanism widely recognised in other tissues to attenuate T-helper-1 associated bacterial-induced inflammation.

Ion Velocity Measurements for the Ionospheric Connections Explorer.

The Ionospheric Connections Explorer (ICON) payload includes an Ion Velocity Meter (IVM) to provide measurements of the ion drift motions, density, temperature and major ion composition at the satellite altitude near 575 km. The primary measurement goal for the IVM is to provide the meridional ion drift perpendicular to the magnetic meridian with an accuracy of 7.5 ms-1 for all daytime conditions encountered by the spacecraft within 15° of the magnetic equator. The IVM will derive this parameter utilizing two sensors, a retarding potential analyzer (RPA) and an ion drift meter (IDM) that have a robust and successful flight heritage. The IVM described here incorporates improvements in the design and operation to produce the most sensitive device that has been fielded to date. It will specify the ion drift vector, from which the component perpendicular to the magnetic field will be derived. In addition it will specify the total ion density, the ion temperature and the fractional ion composition. These data will be used in conjunction with measurements from the other ICON instruments to uncover the important connections between the dynamics of the neutral atmosphere and the ionosphere through the generation of dynamo currents perpendicular to the magnetic field and collisional forces parallel to the magnetic field. Here the configuration and operation of the IVM instrument are described as well as the procedures by which the ion drift velocity is determined. A description of the subsystem characteristics, which allow a determination of the expected uncertainties in the derived parameters, is also given.

An immunoepidemiological approach to asthma: identification of in-vitro T-cell response patterns associated with different wheezing phenotypes in children.

BACKGROUND: Increasing evidence suggests that patterns of T-cell immunity to inhalant allergens in genetically diverse human populations are more heterogeneous than previously assumed, and that covert differences in expression patterns might underlie variations in airway disease phenotypes. We tested this proposition in a community sample of children. METHODS: We analysed data from 172 individuals who had been recruited antenatally to a longitudinal birth cohort study. Of the 194 birth cohort participants, data from the 147 probands (age range 8.6-13.5 years) who consented to blood collection were included along with data from 25 consenting siblings (mean age 11 years [range 7.4-17.4]). We ascertained clinical phenotypes related to asthma and allergy. We measured T-cell responses to allergens and mitogens, together with blood eosinophils and IgE/IgG antibodies, and assessed associations between these indices and clinical phenotypes. FINDINGS: Atopy was associated with allergen-specific T-helper (Th)2 responses dominated by interleukin 4, interleukin 5, interleukin 9, interleukin 13, whereas interleukin 10, tumour necrosis factor alpha, and interferon gamma responses were common to both atopics and non-atopics. The wheal size from skin prick with allergen was positively associated with in-vitro interleukin 5 and interferon gamma responses, and negatively associated with interleukin 10. Asthma, especially in atopics, was strongly associated with eosinophilia/interleukin 5, and bronchial hyper-responsiveness (BHR) was associated with eosinophilia plus polyclonal interferon gamma production. BHR in non-atopics was associated with elevated allergen-specific and polyclonal interleukin 10 production. INTERPRETATION: Parallel immunological and clinical profiling of children identified distinctive immune response patterns related to asthma and wheeze compared with BHR, in atopics non-atopics. Immunological hyper-responsiveness, including within the Th1 cytokine compartment, is identified as a hallmark of BHR. RELEVANCE TO PRACTICE: These findings highlight the heterogeneity of immune response patterns in asthmatic children, including those with seemingly homogeneous Th2-driven atopic asthma. Further elucidation of the covert relationships between wheezing phenotypes and underlying immunophenotypes in this age group will potentially lead to more effective treatments for what is an unexpectedly heterogeneous collection of disease subtypes.

Association between antenatal cytokine production and the development of atopy and asthma at age 6 years.

BACKGROUND: Various lines of evidence suggest that antenatal factors are important in determining susceptibility to atopy and asthma. One possible mechanism is cytokines, production of which in the placenta is high throughout gestation and which protect placental integrity via control of local immunological homoeostasis. We investigated antenatal cytokine concentrations in a prospective birth cohort, intensively monitored for atopy and asthma outcomes at age 6 years. METHODS: Cryopreserved cord-blood serum samples from 407 children were assayed for interleukins 4, 5, 6, 10, 12, and 13, interferon gamma, and tumour necrosis factor alpha (TNFalpha). Associations between family, antenatal, and perinatal factors, cord-blood cytokine concentrations, and atopy or asthma outcomes were analysed by logistic regression. Causal effects of cytokines on outcomes were estimated by propensity scores based on family, antenatal, and perinatal factors. FINDINGS: Detectable cord-blood concentrations of interleukin 4 and interferon gamma were each associated with lower risk of physician-diagnosed asthma (adjusted odds ratios 0.60 [95% CI 0.37-0.99] and 0.60 [0.37-0.97] respectively), current asthma (0.59 [0.33-1.00] and 0.39 [0.22-0.71]), and current wheeze (0.55 [0.32-0.93] and 0.52 [0.31-0.90]) and atopy (sensitisation to some inhalant allergens) outcomes at 6 years. High concentrations of TNFalpha were associated with lower risk of atopy but not with asthma risk. These associations were broadly unaltered by propensity-score adjustment. Maternal smoking was associated with higher risk of both wheeze at 6 years and lower concentrations of interleukin 4 and interferon gamma in cord blood. INTERPRETATION: The mechanism underlying attenuated T-helper-1/T-helper-2 cytokine production in high-risk children also apparently operates in control of cytokine production in the fetoplacental unit. The finding that this mechanism is dysregulated by maternal smoking suggests it is a target for antenatal environmental factors relevant to asthma aetiology.

Early-onset atopy is associated with enhanced lymphocyte cytokine responses in 11-year-old children.

BACKGROUND: Early age at onset of atopy is associated with more severe asthma and increased airway responsiveness (AR); the underlying mechanism is unclear but may involve T cell responses. OBJECTIVE: To test the hypothesis that enhanced T cell responses may be associated with early-onset atopy. METHODS: In a longitudinal study, atopy was determined in infancy and at 6 and 11 years of age. Individuals were categorized as persistent infant-onset atopy (PIOA), early childhood-onset atopy (ECOA) and later childhood-onset atopy (LCOA). At 11 years of age, peripheral blood T cell cytokine responses, AR, exhaled nitric oxide (FE(NO)) and forced expiratory volume in 1 s were determined. RESULTS: The age at onset of atopy was determined for 60 children, of whom 15 had PIOA, 24 had ECOA and 21 had LCOA. An additional 76 children who were never atopic were also included. T cell responses to house dust mite, including interleukin-5, -9, -10 and tumour necrosis factor alpha, were higher among children with PIA and ECOA, and lower in children with LCOA, P<0.05. In contrast, those children with LCOA or who were not atopic had the highest IL-10 response to PHA (P=0.014). Children with PIOA and ECOA, but not LCOA, had higher AR and FE(NO) compared with non-atopic children (P<0.05). The group with PIOA were more likely among the atopic children to be admitted to hospital for asthma (P<0.05) and also had lower %FEV(1) compared with non-atopic children (P=0.023). CONCLUSIONS: Early age at sensitization is associated with enhanced T cell cytokine responses and indices of adverse asthma outcome. T cell cytokine responses might be programmed at the time of initial atopic sensitization.

In vitro synthesis of IgE by human peripheral blood leucocytes. II modulation of IgE B cell activity by isotype-specific regulatory T cells.

IgE and IgG synthesis was demonstrated in cultures of isolated B cells from normal subjects, and those manifesting mild to severe atopy. Titration of autochthonous T cells into B cell cultures revealed both IgE isotype-specific T-help and T-suppression at low and high T:B ratios respectively. Increasing levels of help for IgG synthesis usually accompanied the stepwise addition of the same T cells to autochthonous or allogeneic B cells cultures. Experiments comparing the activity of putative IgE suppressor T cells in autochthonous versus allogeneic B cell cultures indicated that allogeneic interactions per se selectively inhibit IgE B cells. This finding seriously questions earlier conclusions of a causal relationship between suppressor cell deficiency and the expression of the allergic phenotype.

In vitro synthesis of IgE by human peripheral blood leucocytes: relationship to serum titre of leucocyte donor.

A microculture system was developed for in vitro IgE synthesis employing human peripheral blood leucocytes (PBL), comprising 1.0 x 10(6) cells in 1.0 ml serum-supplemented medium, in round-bottomed tubes. Examination of the kinetics of IgE synthesis indicated that production was relatively linear during culture for up to 12 days, and was not susceptible to stimulation with polyclonal B cell mitogen. Employing a standardized 7-day culture period, PBL IgE synthesis was compared within a group of 50 volunteers, comprising normal non-atopic individuals exhibiting serum IgE titres less than 50 units/ml, and moderate atopics with serum titres up to approximately 400 units/ml. PBL IgE synthesis was found to reflect closely the serum IgE status of the cell donor, a feature thus far unique to this culture system, and indicative of the preservation of normal in vivo regulatory mechanisms in the in vitro cultures.

The characteristics of antigen define the cellular source and kinetics of histamine-releasing factor induced by human peripheral-blood mononuclear cells.

Peripheral-blood leucocytes from Dermatophagoides pteronyssinus- and/or Lolium perenne-allergic patients produce in vitro histamine-releasing factor (HRF) in an allergen-specific and concentration-dependent relationship. Maximum production of HRF occurred in cultures containing as little as 10-100 pg/ml crude allergen extract, although a second peak occurred at higher concentrations (10-100 micrograms/ml). While HRF was detectable in 1-hour cultures, maximal production required 24 h in culture. In contrast, HRF induced by streptokinase/streptodornase (SK/SD) was generally maximal after 1 h. Allergen-induced HRF production was almost exclusively associated with monocytes and B cells. In contrast, peripheral-blood T cells were the major source of induced HRF production in cultures containing SK/SD. Histamine-releasing cytokines are apparently produced by different cell populations, the activation of which may be dependent upon the characteristics of the stimulating antigen.

Functional heterogeneity within the human peripheral blood B cell pool engaged in IgE synthesis.

Fractionation of human peripheral blood leukocytes (PBL) B cells by differential sedimentation on percoll gradients separates B cell subpopulations which vary markedly in rates of spontaneous IgE synthesis, in their response to identical populations of autologous T cells and in their response to soluble T cell factors. This B cell fractionation technique often reveals the presence of active IgE-secreting cells which are totally suppressed within unfractionated PBL B cell preparations and greatly improves the efficiency of detection of T cell-responsive, IgE-producing B cells in PBL of atopics.

In vitro synthesis of IgE by human peripheral blood leucocytes. III. Release of pre-formed antibody.

The appearance of IgE in supernatant fluids from cultures of human peripheral blood leucocytes (PBL) is employed in many laboratories as an index of antibody 'synthesis'. This study demonstrates that, unlike IgG, the majority of cell associated IgE is sequestered by PBL in a tightly bound form, which resists extraction via the freeze-thawing (F/T) techniques in current use. A method is presented for the quantitative extraction of cell associated IgE, involving brief acid treatment of whole cells, and is shown to yield up to 100% more IgE than the F/T procedure. The use of this extraction process on PBL before and after culture permits discrimination between release of pre-formed IgE and de novo synthesis, both of which are demonstrated to occur to widely differing degrees in PBL cultures from different donors.

Comparison of IgE expression at the mRNA and protein levels in vitro.

The regulating effects of IL-4 and pokeweed mitogen on IgE synthesis in vitro by human peripheral blood leucocytes has been compared with the corresponding effect of these regulators on the expression of IgE mRNA. The latter was measured by dot blot hybridization with an oligonucleotide coding for a unique six amino acid region of the CH epsilon 2 domain. Specificity of the oligonucleotide probe was established by its inability to hybridize with RNA extracted from HMY-2 (IgG) and XQ-15 (IgM) secreting cell lines whilst producing intense signals with RNA extracted from the IgE secreting cell line U266. Whilst IgE mRNA was detected in RNA extracted from PBL of both atopic and control subjects, spontaneous IgE synthesis was restricted to atopic PBL. IL-4 increased both IgE mRNA and IgE synthesis in all PBL samples but PWM, while significantly increasing IgE mRNA expression either failed to modify IgE synthesis or actively suppressed it. The assay system employed to quantitate IgE synthesis in vitro was shown to be inhibited by both IgE binding factors and IgG anti-IgE autoantibodies which are produced in PBL cultures. IgE mRNA levels might therefore more accurately monitor the regulatory effects of IL-4 and PWM on IgE synthesis than quantitation of the IgE by radioimmunoassay.

A contiguous network of dendritic antigen-presenting cells within the respiratory epithelium.

This study utilises a simple technique to section airway epithelium in a plane parallel to the basement membrane, thus providing a unique plan view of the intra-epithelial cell populations. Immunoperoxidase staining of these tissue sections for class II major histocompatibility complex Ia antigen reveals a virtually contiguous network of Ia-positive dendritic cells (DC) within the epithelium. These DC are shown to be capable of binding inhaled antigens in vivo in a form suitable for presentation to T cells. The strategic location of these cells and the fact that they account for virtually all staining in the airway epithelium during the steady state is convincing evidence that the DC network functions as the 'first line of defence' in surveillance for inhaled antigens and further suggests a major role for the intra-epithelial DC in allergic and infectious disease(s) in the respiratory tract.

Low-level exposure to house dust mites stimulates T-cell responses during early childhood independent of atopy.

BACKGROUND: The immune responses which underlie the expression of allergic symptoms in childhood are believed to be initiated in infancy and early childhood. The kinetics of this response have hardly been researched. OBJECTIVE: To analyse, in an environment with low house dust mite (HDM) exposure levels, the relationship between house dust mite (HDM)-specific T-cell reactivity as expressed by in vitro proliferation of blood mononuclear cells. METHODS: The study comprised a prospective analysis of patterns of allergen-specific T-cell reactivity in a cohort of 19 children, from whom blood samples were obtained in the spring during their second and third years of life. Blood mononuclear cell cultures were established in 200 microL AIM-V serum free medium. Crude house dust mite (HDM) and purified Der p 1 and Der p 2 extracts were used at optimal concentrations, i.e. 100 micrograms/mL for HDM and 30 micrograms/mL for the purified allergens. Tetanus toxoid (0.5 microgram/mL) and ovalbumin (10 micrograms/mL) served as positive controls. A clinical diagnosis of allergy was verified with skin-prick tests. Dust samples were collected from a mattress and/or carpet or sofa in homes, day care centres and day care homes. Major mite allergen levels (Der p 1/Der f 1) in dust were analysed by an enzyme linked immunosorbent assay (ELISA). RESULTS: Specific T-cell responses were seen in the majority of the children against house dust mite (crude HDM extract, Der p 1 and Der p 2). The levels of the house dust mite allergens Der p 1 and Der f 1 were low, i.e. < 0.68 microgram/g fine dust in the homes of the children and the day care centres that they were attending. This indicates that doses of mite antigen well below the suggested sensitization threshold level of 2 micrograms/g dust can induce mite-specific T-cell responses in young children. None of them showed clinical reactivity to house dust mites as indicated by negative skin-prick tests. CONCLUSIONS: The findings suggest that active immunological recognition of environmental allergens and the ensuing initiation of allergen-specific T-cell responses, is a normal part of the 'education' of the immune system in early childhood and can occur even at very low exposure levels. Priming per se does not imply clinically significant sensitivity, however.

Regulation of T-cell sensitization at epithelial surfaces in the respiratory tract: suppression of IgE responses to inhaled antigens by CD3+ Tcr alpha-/beta- lymphocytes (putative gamma/delta T cells).

Repeated exposure of Brown Norway rats to an aerosol of ovalbumin (OVA) induced a state of antigen-specific immunological tolerance, particularly in the IgE isotype. Tolerance was transferable to naive syngeneic animals by inoculation of splenic T cells from tolerant rats. Sequential depletion of tolerant spleen cells by sorting techniques prior to adoptive transfer, employing T-cell subset-specific monoclonal antibodies, indicated that the cells mediating tolerance were CD3+, CD4-, CD5+ and CD8+, but lacked alpha or beta chains in the T-cell receptor (TcR), suggesting that they may be part of the gamma/delta T-cell lineage. Consistent with this suggestion, the sorted population demonstrated considerable enrichment for TcR gamma chain-specific mRNA. As few as 2 x 10(3) cells are sufficient to adoptively transfer tolerance in 200-g adult rats in this model.

"Bystander" amplification of PBMC cytokine responses to seasonal allergen in polysensitized atopic children.

BACKGROUND: Atopic children show increased expression and production of the Th2-associated cytokines IL-4, IL-5, IL-13, and IL-9 from PBMCs after stimulation with allergen, but it has previously not been clearly determined whether the Th2-cytokine production is restricted to the inhalant allergen the child is sensitized to, and whether perennial or seasonal allergens induce different cytokine responses. Our purpose was to determine whether in vitro Th2 cytokine production is specific to the sensitizing allergen, and to compare the cytokine responses to a perennial and a seasonal allergen in monosensitized and polysensitized children. METHODS: Using semiquantitative RT-PCR, we analyzed the expression of the cytokines IL-4, IL-5, IL-13, IL-9, IL-10, and IFN-gamma after stimulation of PBMCs with house-dust-mite (HDM) or ryegrass allergen. The cells were sampled from groups of 6-year-old children sensitized to either HDM (n=20) or ryegrass (n=24), or to both allergens (n=20), as well as from a nonatopic group (n=20). RESULTS: After stimulation with HDM allergen, PBMCs from children sensitized only to HDM expressed increased mRNA levels of the Th2 cytokines, but not of IL-10 and IFN-gamma, whereas ryegrass stimulation did not result in increased cytokine expression. PBMCs from children sensitized to HDM and ryegrass expressed increased Th2 cytokines after stimulation with either of the two allergens. In contrast, PBMCs from children sensitized only to ryegrass did not express increased levels after stimulation with either of the allergens. CONCLUSIONS: The expression of Th2 cytokines after in vitro stimulation of PBMCs from atopic children is specific to the sensitizing allergen, indicating that atopic status per se does not affect the type of T-cell response. In addition, T cells specific to seasonal allergens circulate in the blood out of season only if the child is concomitantly sensitized to a perennial allergen.

Development of immunologic memory against tetanus toxoid and pertactin antigens from the diphtheria-tetanus-pertussis vaccine in atopic versus nonatopic children.

BACKGROUND: Recent findings suggest that a hallmark of the atopic phenotype is reduced capacity to respond to vaccine antigens, as well as to environmental allergens, during infancy. This deficiency, which is most marked for the cytokine IFN-gamma, appears transient but can result in a long-lasting imbalance within T helper cell (T(H)) memory responses to allergens. Indirect evidence suggests that parallel effects may occur within immunologic memory responses against vaccine antigens in atopic children. OBJECTIVE: Our purpose was to compare vaccine antigen-specific T(H) memory responses in atopic and nonatopic children. METHODS: We analyzed specific serum IgG and cytokine responses to pertactin and tetanus antigens as well as to mitogen (PHA) and house dust mite (HDM) allergen in 25 HDM-sensitized atopic and 25 nonatopic 6-year-old children who were vaccinated and boosted with diphtheria-tetanus-pertussis (DTP) vaccine. RESULTS: PBMCs from the atopic subjects produced higher levels of T(H)1 and T(H)2 cytokines to HDM allergen and PHA. Vaccine antibody titers were normal in the atopic subjects; vaccine-specific T(H)2 responses were rarely detectable, yet T(H)1 (IFN-gamma) responses, in particular against tetanus, were frequent and higher in the atopic subjects (121.5 [SE 64.3] vs 8.0 [3.5] pg/mL culture fluid, P =.04). Corresponding pertactin responses were comparable in both groups. CONCLUSIONS: At the completion of the full primer-booster DTP vaccination regimen, levels of vaccine-specific immunity in atopic 6-year-old children are at least equivalent to their nonatopic counterparts, indicating that the transient atopy-associated deficiency in T(H)1 function in childhood can be successfully overcome by appropriate vaccination and boosting regimens.