Blockade of CD28/B7 co-stimulation by mCTLA4-Hγ1 inhibits antigen-induced lung eosinophilia but not Th2 cell development or recruitment in the lung

Nicola Harris, Chloë Campbell, Graham Le Gros, Franca Ronchese

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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-Hγ1) which binds to B7 molecules on antigen-presenting cells, thereby preventing their interaction with T cell-expressed CD28. mCTLA4-Hγ1-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-Hγ1-transgenic and normal mice. Also, lung lymphocytes from immunized mCTLA4-Hγ1-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-Hγ1. We conclude 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.

Original languageEnglish
Pages (from-to)155-161
Number of pages7
JournalEuropean Journal of Immunology
Volume27
Issue number1
DOIs
Publication statusPublished - 1 Jan 1997
Externally publishedYes

Keywords

  • Co-stimulation
  • Eosinophil
  • Inflammation
  • Lung immune response
  • T cell

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