The role of natural CD4+CD25+ regulatory T (T reg) cells in the control of allergic asthma remains poorly understood. We explore the impact of T reg cell depletion on the allergic response in mice susceptible (A/J) or comparatively resistant (C3H) to the development of allergen-induced airway hyperresponsiveness (AHR). In C3H mice, anti-CD25–mediated T reg cell depletion before house dust mite treatment increased several features of the allergic diathesis (AHR, eosinophilia, and IgE), which was concomitant with elevated T helper type 2 (Th2) cytokine production. In similarly T reg cell–depleted A/J mice, we observed a moderate increase in airway eosinophilia but no effects on AHR, IgE levels, or Th2 cytokine synthesis. As our experiments suggested that T reg cell depletion in C3H mice before sensitization was sufficient to enhance the allergic phenotype, we characterized dendritic cells (DCs) in T reg cell–depleted C3H mice. T reg cell–depleted mice had increased numbers of pulmonary myeloid DCs with elevated expression of major histocompatibility complex class II, CD80, and CD86. Moreover, DCs from T reg cell–depleted mice demonstrated an increased capacity to stimulate T cell proliferation and Th2 cytokine production, which was concomitant with reduced IL-12 expression. These data suggest that resistance to allergen-driven AHR is mediated in part by CD4+CD25+ T reg cell suppression of DC activation and that the absence of this regulatory pathway contributes to susceptibility.

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The ovaries of endoparasitic species of braconid and ichneumonid wasps contain large numbers of polydnavirus (PDV) virions that replicate in specialized calyx cells of the ovaries and are injected into the host larva during parasitization. In the braconid wasp Cotesia congregata that parasitizes the tobacco hornworm, Manduca sexta, the total amount of viral DNA present in the ovaries was determined to be 25-75 ng. Analysis of viral DNA on 0.4% agarose gels showed that the genome was comprised of 15-20 circles of double-stranded DNA. SDS-PAGE analyses showed that a large number (>30) of structural polypeptides were present in the virions, and analysis of the venom likewise showed that multiple components were present. The major size classes of venom proteins differed from those present in the PDV. However, Western blots using polyclonal PDV antibodies showed that some cross-reacting PDV-like proteins were present in the venom, perhaps explaining the mild PDV-enhancing effect of the venom. Injection of PDV into unparasitized larvae provoked pronounced alterations in their growth, development, pigmentation, and hemolymph proteins. A densely staining band of hemolymph proteins of approximately 18-20 kD appeared in large amounts relative to other hemolymph proteins several days following injection of PDV; this band was undetectable in naturally parasitized larvae. Eggs which had been washed extensively to remove PDVs were encapsulated following injection, but development of the host still was disrupted, usually in the post-wandering prepupal stage. Thus,

Although IL-4 signals through two receptors, IL-4Rα/common γ-chain (γc) and IL-4Rα/IL-13Rα1, and only the latter is also activated by IL-13, IL-13 contributes more than IL-4 to goblet cell hyperplasia and airway hyperresponsiveness in murine asthma. To determine whether unique gene induction by IL-13 might contribute to its greater proasthmatic effects, mice were inoculated intratracheally with IL-4 or IL-13, and pulmonary gene induction was compared by gene microarray and real-time PCR. Only the collagen α2 type VI (Ca2T6) gene and three small proline-rich protein (SPRR) genes were reproducibly induced >4-fold more by IL-13 than by IL-4. Preferential IL-13 gene induction was not attributable to B cells, T cells, or differences in cytokine potency. IL-4 signaling through IL-4Rα/γc suppresses Ca2T6 and SPRR gene expression in normal mice and induces these genes in RAG2/γc-deficient mice. Although IL-4, but not IL-13, induces IL-12 and IFN-γ, which suppress many effects of IL-4, IL-12 suppresses only the Ca2T6 gene, and IL-4-induced IFN-γ production does not suppress the Ca2T6 or SPRR genes. Thus, IL-4 induces genes in addition to IL-12 that suppress STAT6-mediated SPRR gene induction. These results provide a potential explanation for the dominant role of IL-13 in induction of goblet cell hyperplasia and airway hyperresponsiveness in asthma.