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Biomedical subjects

S L Prescott

Publications and source records attributed to S L Prescott.

34 records · Page 2Linked to original sources
PubMed2002

Cellular immune responses to ovalbumin and house dust mite in egg-allergic children.

BACKGROUND: Although IgE-mediated food (egg) allergy is typically lost with age the underlying immune mechanisms are not understood, particularly in relation to the development of persistent IgE-mediated aeroallergen sensitivity. METHODS: Lymphoproliferation and cytokine responses (IL-5, IL-10, IL-13 and IFN-gamma) to house dust mite (HDM) allergen and egg ovalbumin (OVA) were assessed using peripheral blood mononuclear cells (PBMC) from children aged 6 months to 5 years (n = 59) with acute IgE-mediated egg allergy (urticaria and angiedema or anaphylaxis), as confirmed by positive skin prick testing (SPT). Of these 46 had positive SPT on the day of blood collection and 13 had outgrown egg allergy (negative SPT and successful egg challenge). Where possible, responses were compared with previous data from nonallergic children of similar ages (n = 107). RESULTS: Transient lymphoproliferative responses to OVA were seen in both egg-allergic and nonallergic children, but were more marked and more prolonged in egg-allergic children. Younger egg-allergic children (< 18 months) showed a mixed Th0 cytokine response to OVA, with readily detectable IFN-gamma, IL-5, IL-13 IL-10. Although IL-13 and IL-5 responses (OVA) correlated in younger egg-allergic children, there was a dissociation of these Th2 responses with age. Loss of clinical reactivity to egg was associated with almost complete loss of IL-5 responses and OVA-specific lymphoproliferation. Although IL-13 levels tended to be lower with age, this was not significant. Strong IFN-gamma and IL-10 responses to OVA persisted in older children after loss of OVA-specific lymphoproliferation. Lymphoproliferative responses to HDM also developed earlier in egg-allergic children compared with nonallergic children. Th1 (IFN-gamma) responses to HDM were largely below detection prior to 18 months of age, but increased significantly with age. In egg-allergic children Th2 (IL-5, IL-13) HDM responses also progressively increased with age. At 3 years of age almost all egg-allergic children had positive SPT to HDM and positive lymphoproliferative responses to HDM, with strong Th1 and Th2 (Th0) cytokine production. CONCLUSIONS: IL-5 responses (rather than IL-13) responses most closely reflected clinical food allergy, with dissociation of IL-5 and IL-13 responses in older and egg-tolerant children. In this population, food and aeroallergen sensitivity was not associated with inability to produce IFN-gamma, but rather with mixed Th2 and Th1 (Th0) responses. Strong IL-10 and IFN-gamma responses where associated with the development of tolerance, suggesting persistent 'regulatory' populations of OVA-specific T cells, rather than clonal deletion of OVA responsive T-cells.

Animals↗
PubMed2000

Effects of maternal allergen-specific IgG in cord blood on early postnatal development of allergen-specific T-cell immunity.

BACKGROUND: A wide body of epidemiologic evidence indicates that as yet unknown maternal factor(s) can influence susceptibility to allergic disease in the offspring. It is also well established that the induction of allergen-specific T-cell memory is frequently initiated in utero, and it is likely that maternal factors exert their influence during this period. METHODS: This study examines the relationship between maternally derived allergen-specific IgG subclass antibodies and cellular immune responses (lymphoproliferation and cytokine production) against the same allergens in 49 subjects tested at birth and at 2 years of age. Polyclonal production of the Th1 cytokine IFN-gamma was also examined in the cord-blood samples. RESULTS: At birth, there were positive correlations between both house-dust mite (HDM)- and ovalbumin (OVA)-specific IgG subclass levels in cord blood, maternal atopy, and the magnitude of perinatal lymphoproliferative responses to respective allergens. Inverse relationships were also observed between cord-blood IgG antibody titres and allergen-specific production of some Th2 cytokines. However, there were no consistent relationships between cord-blood allergen-specific IgG antibodies and subsequent immune responses to allergens when the same subjects were retested at 2 years of age. An inverse relationship was observed between maternal history of atopy and perinatal IFN-gamma production capacity. CONCLUSIONS: Our results suggest that transplacental transfer of allergen-specific IgG antibody is unlikely to be a major mechanism for maternal regulation of allergen-specific immunity in infancy. An alternative possibility is that maternal effects may operate by influencing IFN-gamma production by T cells in the offspring.

Allergens↗
PubMed2000

Primary sensitization to inhalant allergens.

The neonatal T-cell system is capable of responding to allergens at birth, indicating the occurrence of prenatal sensitization, and the cytokine profile of these responses is skewed towards the Th-2 type. This response is further modified by postnatal exposure to different types of allergens. In relation to inhalant allergen (employed by HDM) the low level fetal Th-2 responses in non-atopics appear to be down-regulated rapidly after birth, parallel to an increase in allergen-specific IFN-gamma production. In contrast, atopics appear to consolidate their initial Th-2 responses, and around the age of 6 exhibit a cytokine response profile similar to the adult pattern. A pre-existing deficiency in IFN-gamma production may be one of the key factors determining the postnatal persistence of Th-2 responses in atopics.

Allergens↗
PubMed1999

Development of allergen-specific T-cell memory in atopic and normal children.

BACKGROUND: In the past 20-30 years, there has been an increase in prevalence of allergic respiratory diseases, particularly amongst children. This study is a prospective analysis of the postnatal maturation of T-helper cell (Th) responses to aeroallergens in atopic and non-atopic infants. METHODS: We measured mononuclear-cell proliferative and cytokine responses to specific allergens and tetanus toxoid in blood samples from atopic and non-atopic infants every 6 months from birth to 2 years of age. Cytokine analyses of responses to housedust-mite allergen used ELISA and reverse-transcriptase PCR. We also measured responses to Fel d1 (cat allergen) and tetanus toxoid. FINDINGS: Samples from 18 atopic and 13 non-atopic infants showed low-level Th2-skewed allergen-specific responses at birth, with little accompanying specific interferon-gamma production. Neonatal Th2 responses were lower in the atopic group than in the non-atopic group; the differences were significant for interleukin-4 (mRNA: beta-actin ratio 0.48 [SE 0.15] vs 0.15 [0.06], p=0.049), interleukin-6 (4750 [48] vs 1352 [51] pg/mL culture fluid, p=0.003), interleukin-10 (1162 [228] vs 485 [89], p=0.015), and interleukin-13 (7.1 [0.9] vs 0.9 [0.3], p=0.008). There was rapid suppression of Th2 responses during the first year of life in non-atopic children, but there was consolidation of responses in atopic children, associated with defective neonatal interferon-gamma production. INTERPRETATION: The continuation of fetal allergen-specific Th2 responses during infancy is a defining feature of the inductive phase of atopic disease, and is associated with decreased capacity for production of the Th1 cytokine interferon y by atopic neonates. These findings provide a plausible mechanism for persistence of the fetal Th2 responses during early childhood in atopic individuals and subsequent expression of disease.

Allergens↗
PubMed1999

Microbial stimulation as an aetiologic factor in atopic disease.

Epidemiologic evidence from various sources suggests that exposure to microbial stimuli during early childhood can influence the induction and expression of atopic diseases, particularly in the respiratory tract. Moreover, these effects may have long-lasting consequences in relation to expression of the atopic phenotype in adulthood. This review discusses key aspects of this evidence in relation to the underlying mechanisms which regulate T-helper (Th)-cell function; in particular, the generation of Th-memory cells responsive to inhalant allergens.

Adjuvants, Immunologic↗
PubMed1998

Transplacental priming of the human immune system to environmental allergens: universal skewing of initial T cell responses toward the Th2 cytokine profile.

The expression of Th2-skewed immunity against soluble protein Ags present in the normal environment is recognized as the primary cause of allergic inflammation in atopics. In contrast, nonallergic normal individuals display low level Th1-skewed immunity against the same Ags ("allergens"), which is perceived as conferring protection against Th2-dependent allergic sensitization. The type of T cell memory that develops against these Ags is currently believed to be the result of complex interactions between environmental and genetic susceptibility factors, which occur postnatally when the naive immune system directly confronts the outside environment. The results of the present study challenge this general concept. We demonstrate here for the first time that Th2-skewed responses to common environmental allergens, comprising IL-4, IL-5, IL-6, IL-9, and IL-13, are present in virtually all newborn infants and are dominated by high level production of IL-10. Moreover, these responses are demonstrable within 24 h of culture initiation, arguing against a significant contribution from covert in vitro T cell priming and/or differentiation. These findings imply that the key etiologic factor in atopic disease may not be the initial acquisition of allergen-specific Th2-skewed immunity per se, but instead may be the efficiency of immune deviation mechanisms, which in normal (nonatopic) individuals redirect these fetal immune responses toward the Th1 cytokine phenotype.

Allergens↗
PubMed1998

Reciprocal age-related patterns of allergen-specific T-cell immunity in normal vs. atopic infants.

By adulthood there is almost universal immunological memory to aeroallergens, and the presence of allergic disease appears to be related to the nature of the underlying T-helper (Th) cell cytokine responses. The hypothesis of this study is that adult patterns of allergen specific Th-cell memory (Th-2 polarized in atopics vs. Th1 in non-atopics) can be determined in early infancy. Mononuclear cell cytokine responses to house-dust mite were measured at 6-monthly intervals from birth to 2 years of age, using ELISA (IL-10, IL-13, IFN-gamma) and sqRT/PCR (IL-4, IL-5, IL-9, IFN-gamma) in normal infants (n = 14) with no family history or allergic symptoms, and infants with a family history and definite atopy by 2 years (n = 16). Both normals and atopics showed low-level Th2 skewed allergen-specific responses at birth with little accompanying IFN-gamma. The Th2 responses to house-dust mite were higher in normal newborns, who then show a rapid downregulation of these responses in the first year of life. Atopic infants instead show a consolidation of their neonatal patterns of Th2 polarized allergen specific immunity. Earlier studies indicate that neonates at high risk of atopy display diminished capacity for production of the Th1 cytokine IFN-gamma. The present study suggests for the first time that neonates who subsequently develop atopy also initially have reduced capacity to mount Th2 responses. However, in contrast to non-atopics who selectively downregulate their fetal Th2 polarized allergen-specific responses, atopic children display age-associated upregulation of Th2 immunity.

Aging↗
PubMed1997

TH2-polarized immunological memory to inhalant allergens in atopics is established during infancy and early childhood.

BACKGROUND: There is increasing evidence that the T-cell reactivity to environmental allergens underlying expression of allergic disease in adulthood, develops initially during childhood. However, there is little information available on the kinetics of these early responses, or on the patterns of cytokine production during this period. OBJECTIVE: The purpose of this study was twofold: to obtain further information on the reported differences between responses to food versus inhalant allergens during early childhood, and to ascertain the age-range over which T-cell responses to inhalant allergens become polarized towards the TH2 cytokine profile, in potentially atopic children. METHODS: In vitro cytokine responses to house dust mite (HDM) and egg (OVA) were assessed by semiquantitative RT-PCR in panels of 2- and 5-year-old children and adults; lymphoproliferative responses to OVA were subjected to epitope analysis. RESULTS: At age 2 years IL-4/IL-5 responses to HDM grouped with positive atopic family history, and by age 5 years cytokine responses correlated strongly with individual SPT reactivity to HDM. In contrast, OVA responses were restricted to weak and transient IL-5 signals in the 2-year-old family history positive group. Lymphoproliferation assays performed in parallel indicate a log-scale greater postnatal expansion of T-cell reactivity to the inhalant allergen; preliminary epitope analysis of OVA responses indicate that the number of OVA epitopes recognised decrease during early childhood. CONCLUSIONS: Inhalant allergen-specific in vitro cytokine production associated with positive skin-prick test (SPT) reactions, one of the hallmarks of adult atopy, manifests in children at or before 5 years of age; additionally, cytokine responses in SPT negative 5 year-olds are restricted to IFNgamma, as per normal adults. In contrast, T-cell responses to a typical food allergen appear to be deleted during early childhood.

Age Factors↗
PubMed1988

A randomized controlled trial of the effect on blood pressure of dietary non-meat protein versus meat protein in normotensive omnivores.

1. A randomized, controlled trial was carried out to examine whether changes in type and amount of dietary protein were responsible for earlier observations of blood-pressure-lowering effects of lacto-ovo-vegetarian diets. 2. Sixty-four subjects were pair-matched for sex, age, weight and sitting systolic blood pressure, and were randomly allocated to receive one of two types of protein supplement: one containing proteins from meat, the other proteins from non-meat sources. The supplements were balanced in terms of other nutrients. Consumption of other meat, poultry or fish was prohibited. 3. Sitting and standing blood pressures, weight, dietary intakes and plasma and urinary electrolytes were measured at regular intervals during the 12 weeks of trial. Urinary 3-methylhistidine was used as a measure of compliance. 4. Fifty subjects completed the trial. There were no statistically significant blood pressure differences between groups either at baseline or at end-of-trial, neither were there any substantive differences in mean blood pressure changes between baseline and end-of-trial. 3-Methyl-histidine excretion was significantly lower in subjects on the non-meat diet. 5. The results suggest that the protein components of the lacto-ovo-vegetarian diet are not responsible for the blood-pressure-lowering effects of that diet.

Adolescent↗
PubMed1987

Controlled study of the effects of dietary protein on blood pressure in normotensive humans.

1. The object of this study was to determine whether meat protein per se is responsible for the higher blood pressures (BP) in omnivores compared with vegetarians. 2. Assessments were made by a double blind randomized control trial in 64 normotensive volunteers recruited from Royal Perth Hospital staff. 3. All volunteers were given a 'meat' substitute during the 2 week control period. Randomization was then introduced into two dietary groups: the first remained on the 'meat' substitute, and the other received a 'non-meat' substitute of vegetable protein, for the remaining 12 weeks of the trial. 4. The content of 'meat' and 'non-meat' substitute was designed quantitatively and qualitatively to represent the protein intake in recently studied diets of Australian omnivores and ovo-lacto vegetarians, respectively. The levels of fats (saturated and unsaturated), fibre, energy, Na+, K+, Mg2+, Ca2+ and carbohydrate in the intervention diets were similar. 5. These dietary changes were not associated with any significant changes in BP. Significantly lower urinary 3-methyl histidine excretions in volunteers receiving 'non-meat' supplements compared with the 'meat' eaters confirmed the dietary changes. 6. It was concluded that BP differences between omnivores and accultured vegetarians are unlikely to be due to differences in protein intake.

Adolescent↗
PubMedDate not supplied

Developing patterns of T cell memory to environmental allergens in the first two years of life.

Several recent studies have demonstrated cord blood mononuclear cell (CBMC) proliferation in response to food and inhalant allergens, suggesting that initial T-cell-priming may occur in utero. The findings below from an ongoing prospective study on 60 subjects provide initial information on the nature of accompanying T cell cytokine responses. We demonstrate CBMC proliferation following culture with house dust mite and ovalbumin (OVA) in 47 and 42% of subjects, respectively, compared to an overall rate of 3% for tetanus toxoid; the frequencies of these responses were comparable in neonates with and without atopic family history (FH). With the exception of IL-10, analysis of cytokine responses in allergen-stimulated cultures of CBMCs required the use of semiquantitative RT-PCR, which revealed low-level IL-4 and/or IL-5 mRNA production, in particular a 50% IL-5 response rate to OVA in FH-positive neonates. IFN-gamma responses were less frequent and required higher PCR cycle numbers for detection. Preliminary analysis of culture supernatants from a subgroup of CBMCs indicate high-level allergen-specific IL-10 responses in both FH-negative and -positive subjects, detectable by ELISA. Parallel PCR studies on MCs from 27 children (mean age 18 months) indicated a clear segregation at this age on the basis of FH, with Th0-like or mixed Th1/Th2 responses (IL-5 plus IFN-gamma) which were mainly restricted to the FH-positive group.

Allergens↗