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 bacterialinduced inflammation.

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-γ 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-γ) which were mainly restricted to the FH-positive group.

There is mounting evidence that antenatal factors could be important in children who develop atopy and asthma. Immunologic processes appear to operate in early infancy when challenged by exposure to environmental allergens. One possible mechanism is an alteration in cytokines, which are produced in the placenta throughout gestation and serve to protect the placenta by controlling local immunologic events. The investigators measured levels of several cytokines in cord blood in a prospective birth cohort of 407 children. They included interleukins 4, 5, 6, 10, 12, and 13; interferon-␥; and tumor necrosis factor-alpha (TNF␣). At age 6 years, 34% of the study group had been diagnosed with asthma, 21% currently had asthma, and 40% had 1 or more positive skin-prick tests. The most commonly detected cytokines were interleukins 4 (73%), 6 (69%), and 13 (46%) of cord blood samples, and interferon-␥ (37%). Higher levels of interleukins 6 and 10 were associated with perinatal stress as reflected by the need for assisted delivery and lower Apgar scores. There was, however, no relationship between cytokine levels and pregnancy complications that could correlate with chronic fetal stress. Maternal smoking during pregnancy correlated with lower cord blood levels of interleukin 4 and interferon-␥, and also with a higher risk of wheezing at age 6. Higher concentrations of interferon 4, interferon-␥, and TNF␣ were related to a lower risk of physician-diagnosed asthma and atopy at age 6 years. This study provides evidence of attenuated production of cytokines characteristic of peripheral blood T cells in infants at risk of asthma and atopy. The genetic factors determining the expression of peripheral blood T cells in atopic children could also control cytokine production by placental trophoblasts. In addition, cytokine production could be sensitive to adverse environmental exposures such as maternal smoking during pregnancy.

The assessment of IgE production in cultures of T- and B-cells from peripheral blood is proving a useful tool to probe IgE immunoregulation in human atopies. The present study contrasts secretion and synthesis as indices of IgE production, and demonstrates that these measures yield comparable data upon the magnitude and direction of regulatory T-cell effects (help vs. suppression) in severe atopies. The majority of peripheral blood B-cell samples from the atopies in this study exhibited spontaneous IgE synthesis and secretion, and in vitro T-cell help and suppression were observed with equal frequency within the sample population. Repeated testing of individual atopies indicated that the direction of T-cell effects remained stable in some (but not all) atopies over periods as long as 3 years.

Summary The functional characteristics of peritoneal cells (PC's) acquired in response to infection with Nematospiroides dubius were studied to identify changes which could be associated with the high level, long‐term survival of this parasite or explain its transient immunosuppressive properties. The number of cells in the peritoneal cavity increased steadily during the infection, and the population displayed a transient hyperreponsiveness to inflammatory stimulation. N. dubius did not affect the ability of antigen‐pulsed PC's to induce humoral responses or delayed‐type hypersensitivity (DTH) in primed recipients, but lymphoproliferative responses induced in vitro were depressed by PC's from infected donors. In addition, unpulsed PC's from N. dubius‐infected mice depressed proliferative responses to parasite antigens by autologous mesenteric lymph node cells. These effects are attributable to increased lymphocytostatic activity in the PC's, which peaked one week after infection and correlated with the expansion of a population of large plastic‐adherent vacuolated cells with elevated acid phosphatase activity (activated macrophages). Comparable inhibitory cells did not develop in the same period of time during a short‐lived infection with Nippostrongylus brasitiensis.