Showing papers by "Nicola L. Harris published in 1997"
TL;DR: CD80 blockade prevented antigen-induced accumulation of eosinophils and lymphocytes in the lung of immunized mice, but did not block antigen induced systemic blood eOSinophilia or IgE antibody production.
Abstract: CD80 and CD86 (B7-1 and B7-2) are the ligands on antigen-presenting cells (APCs) which bind CD28 and deliver the costimulatory signals necessary for T cell activation. The reasons for the existence of two CD28 binding molecules are not well understood. We created a mutant version of CTLA4-Ig that could selectively bind CD80 and block CD28-CD80 interaction but leave CD28-CD86 binding intact. CD80 blockade prevented antigen-induced accumulation of eosinophils and lymphocytes in the lung of immunized mice, but did not block antigen induced systemic blood eosinophilia or IgE antibody production. No preferential expression of CD80 could be demonstrated on a population of lung APC consisting mainly of macrophages. These results indicate that CD80 costimulation is not necessary for the induction of Th2 immune responses but rather for the maintenance or amplification of lung inflammatory responses.
121 citations
TL;DR: It is concluded that mCTLA4‐Hγ1 can efficiently block the production of IL‐5 during in vivo responses and inhibit eosinophil recruitment, but that it does not block the development of CD4+ T cells into Th2 cells with the potential to secrete IL‐ 5.
Abstract: We have studied the role of the CD28/B7 co-stimulatory pathway in the development of a Th2-type lung immune response. Mice injected two or three times intraperitoneally with ovalbumin in alum adjuvant and then re-exposed to the same antigen by intranasal (i.n.) inoculation show infiltration of the lung tissue and appearance in the broncho-alveolar lavage (BAL) fluid of significant numbers of eosinophils and lymphocytes, in a pattern which is reminiscent of asthmatic inflammation. The accumulation of eosinophils in the airways is completely dependent on interleukin (IL)-5 secretion by CD4+ T cells. We have used mice transgenic for a soluble form of murine CTLA-4 (mCTLA4-Hgamma1) which binds to B7 molecules on antigen-presenting cells, thereby preventing their interaction with T cell-expressed CD28. mCTLA4-Hgamma1-transgenic mice immunized intraperitoneally and challenged i.n. with ovalbumin failed to generate any eosinophil infiltration, suggesting that little or no IL-5 was secreted in the lungs of these mice. In contrast with the complete lack of eosinophils, the numbers and phenotypes of infiltrating lymphocytes were comparable in the lungs of mCTLA4-Hgamma1-transgenic and normal mice. Also, lung lymphocytes from immunized mCTLA4-Hgamma1-transgenic and normal mice could be shown to secrete comparable amounts of IL-4 and IL-5 when stimulated in culture in the absence of mCTLA4-Hgamma1. We conclude that mCTLA4-Hgamma1 can efficiently block the production of IL-5 during in vivo responses and inhibit eosinophil recruitment, but that it does not block the development of CD4+ T cells into Th2 cells with the potential to secrete IL-5.
55 citations