Responses to the house dust mite during infancy may be important determinants of asthma in susceptible individuals. This study assessed early IgG subclass antibody responses to Dermatophagoides pteronyssinus in children of atopic parents. Sixteen atopic and 15 non-atopic children were selected from a birth cohort, and atopic status was established according to follow up over the first two years. IgG1 and IgG4 antibodies to D pteronyssinus were measured by enzyme linked immunosorbent assay at 7 days and 3, 6, 12, and 24 months. In all children D pteronyssinus IgG1 fell at 3 months (indicating maternal antibody loss), rose progressively to 12 months, and waned at 24 months. D pteronyssinus IgG4 was only detectable at 7 days. Children who were atopic by 2 years and therefore at greater risk of asthma, tended to have higher D pteronyssinus IgG1 at 6 and 12 months. These data suggest greater exposure or responsiveness to dust mite during infancy than in the second year.
Human primary effector T cells were analyzed for their susceptibility to anti-CD3-induced activation-induced cell death (AICD). Th1 and Tc1 cells were more susceptible to AICD than their type 2 counterparts. Type 1 and type 2 subsets were also found to be differentially susceptible to CD95-mediated apoptosis, although cell-surface expression of CD95 and CD95L was at similar levels on all subsets. A role for CD95 in AICD was confirmed by the addition of anti-CD95L antibodies that partially abrogated AICD. Residual apoptosis could not be accounted for by TNF-alpha/TNFR interactions because although type 1 cells secreted more TNF-alpha than type 2 cells, the addition of TNFR:Fc fusion protein did not inhibit AICD. Instead, a reduction in AICD was observed in the presence of EGTA or concanamycin A. The inhibition of apoptosis by a granzyme B inhibitor z-AAD-CMK in Tc1 cells further indicated an involvement of the granule exocytosis mechanism in AICD.
Since the discovery ofIgE in the late 1960s (Ishizaka, Ishizaka & Hornbrook, 1966; Johansson & Bennich, 1967) several animal models have been developed to study the regulation of IgE. IgE responses in atopic people are typically long lived and can be maintained when they are no longer exposed to allergen as in hay fever patients outside the pollen season. Such responses have proved difficult to produce in most species, with the exception of mice, and after an initial burst of IgE when first immunized, the response generated is rapidly suppressed. The artificial induction of IgE responses in rodents has required the use of adjuvants such as aluminium hydroxide and Bordatella pertussis or concomitant nematode infection (Jarrett & Stewart, 1972). T cells play a central role in regulating IgE responses (Okumura & Tada, 197 la; Katona, Urban & Finkelman, 1988), and as well as providing help for IgE B cells, they are capable of suppressing both primary and secondary IgE responses (Okumura & Tada, 1971b; Holt, Batty & Turner, 1981a). Thus two opposing functions for T cells in IgE regulation can be seen. These effects are mediated at least in part by T cell-derived cytokines. High levels of interleukin-4 (IL-4) were found to potentiate IgE synthesis from lipopolysaccharide (LPS) stimulated murine B cells in vitro (Coffman & Carty, 1986) and this effect could be antagonized with interferon-gamma (IFN-y) (Snapper & Paul, 1987). Anti-IL-4 antibody (Finkelman et al., 1986, 1988a) or IFN-y (Finkelman et al., 1988b) both suppress antigen and Nippostrongylus braziliensis-induced IgE responses in vivo. With N. braziliensis infestation, IgE levels spontaneously decline following worm expulsion but similar effects were also seen with anti-IL-4 and IFN-y in Heligmosomoides polygyrusinfested mice, where the worm is not expelled and IgE levels do not fall (Finkelman et al., 1990). The secondary IgE response produced with antigen and Al(OH)3 was largely but not completely inhibited with anti-IL-4 (Finkelman et al., 1990); these investigators conclude that the role of IL-4 in the maintenance of an IgE response is to recruit
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