Signal transducers and activators of transcription 6 (STAT6) is essential for interleukin 4–mediated responses, including class switching to IgE and induction of type 2 T helper cells. To investigate the role of STAT6 in allergic asthma in vivo, we developed a murine model of allergen-induced airway inflammation. Repeated exposure of actively immunized C57BL/6 mice to ovalbumin (OVA) aerosol increased the level of serum IgE, the number of eosinophils in bronchoalveolar lavage (BAL) fluid, and airway reactivity. Histological analysis revealed peribronchial inflammation with pulmonary eosinophilia in OVA-treated mice. In STAT6-deficient (STAT6−/−) C57BL/6 mice treated in the same fashion, there were no eosinophilia in BAL and significantly less peribronchial inflammation than in wild-type mice. Moreover STAT6−/− mice had much less airway reactivity than wild-type mice. These findings suggest that STAT6 plays a crucial role in the pathogenesis of allergen-induced airway inflammation.

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The murine acquired immunodeficiency syndrome (MAIDS) caused by a defective murine leukemia virus produces severe immunodeficiency with abnormal lymphoproliferation and hypergammaglobulinemia. The presence of both CD4+ T cells and B cells is critical for the development of this disease. Remarkably elevated mRNA expression for IFN-gamma and IL-10 was observed in spleen cells of C57BL/6 mice starting from the early phase of viral infection. IFN-gamma production was induced by spleen cells from virus-infected mice upon stimulation with concanavalin A or lipopolysaccharide in both the early and late phases of MAIDS progression. When mice that had been passively administered anti-IFN-gamma mAb were infected with the virus, the development and progression of lymphadenopathy, immunodeficiency and elevated levels of serum IgG2a associated with MAIDS were delayed. Treatment with anti-IL-4 or anti-IL-10 mAb in place of anti-IFN-gamma mAb did not induce the delayed progression of MAIDS. These data support the concept that IFN-gamma-dependent pathway may be involved in the development of MAIDS.

ABSTRACT. Murine tracheal epithelial cell lines, TM01and TM02-3, were established from a primary culture of tracheal cells of adult transgenic mice bearing a temperature-sensitive simian virus (SV40) large T-antigen gene. Both TM01and TM02-3 cells, which grew until con fluent monolayers were formed, maintained tight contact with neighboring cells, and retained the characteristics of epithelial cells with microvilli on the surface. These cells grew at a permissive temperature (33°C), but did not at a nonpermissive temperature (39°C), indicating that TM01and TM02-3 cells undergo temperature-sensitive growth. Large T-antigen was expressed only in the nuclei at 33°C. Sepharose CL-4B column chromatography using a 14C-glucosamine hydrochloride, indicating that both cells produced high molecular weight glycoconjugates, and suggesting that these cells may originate from mucus-producing cells. TM01cells expressed intercellular adhesion molecular-1 (ICAM-1) in both unstimulated and stimulated (1,000 U/ml tumor necrosis factor-a and 500 U/ml interferon-^) conditions, whereas TM02-3cells expressed ICAM-1only under stimulated conditions. Weconclude that these cell lines mayserve as a useful model to study the tracheal cell functions under defined in vitro conditions. The respiratory tract is protected by mucus, which consists of glycoconjugates, proteins and lipids (1). Mucus (SV40) large T-antigen gene (9-ll). It has also been indicated that a transgenic mouse which harbors the temperature-sensitive SV40 (tsSV40) large T-antigen gene is useful for establishing culture cells from tissues that have proved difficult to culture in vitro (12-18). Recently, we reported the establishment of gastric surface mucus cell lines, GSM06and GSM10, which have specific functions, from the primary culture of gastric mucosal cells of the transgenic mice harboring the tsSV40 large T-antigen gene (17, 19, 20).In the present study, we succeeded in establishing tracheal epithelial cell lines TM01 and TM02-3, which produce high molecular weight glycoconjugates from transgenic mice bearing the tsSV40 large T-antigen gene. In addition, these cells express intracellular adhesion molecule-1 (ICAM-1) on their surface.

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Infection of C57BL/6 mice with LP-BM5 murine leukemia virus (MuLV) leads to the development of murine acquired immunodeficiency syndrome (MAIDS) characterized by abnormal lymphoproliferation, hypergammaglobulinemia and severe immunodeficiency. Progression of MAIDS is delayed in X chromosome-linked immunodeficient (XID) mice, which have an abnormality of Bruton's tyrosine kinase (Btk) and lack functionally mature B cells including CD5+ B cells. In this study, we report the following four major findings. (i) Susceptibility to disease induction is not reconstituted by transfer of CD5+ B cells to XID mice. (ii) Spleen cells from asymptomatic XID mice are able to transmit MAIDS to wild-type mice. (iii) MAIDS can be transmitted to XID mice with the transfer of B cells, but not T cells, from C57BL/6 mice with MAIDS. (iv) Cells which undergo massive lymphoproliferation in XID mice with MAIDS by cell transfer are of host origin, but are not from the donor. We suggest from these results that a B cell subpopulation that is impaired in XID mice plays an important role in the initiation of MAIDS.

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