| Autor: |
Humphreys IR; Center for Molecular Microbiology and Infection, Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, United Kingdom., Edwards L, Walzl G, Rae AJ, Dougan G, Hill S, Hussell T |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2003 Jun 15; Vol. 170 (12), pp. 6125-32. |
| DOI: |
10.4049/jimmunol.170.12.6125 |
| Abstrakt: |
Pulmonary eosinophilia induced in C57BL/6 mice after Cryptococcus neoformans infection is driven by CD4(+) Th2 cells. The immunological mechanisms that protect against eosinophilia are not fully understood. Interaction of OX40 (CD134) and its ligand, OX40L, has been implicated in T cell activation and cell migration. Unlike CD28, OX40 is only expressed on T cells 1-2 days after Ag activation. Manipulation of this pathway would therefore target recently activated T cells, leaving the naive repertoire unaffected. In this study, we show that engagement of OX40 by an OX40L:Ig fusion protein drives IFN-gamma production by CD4(+) T cells and reduces eosinophilia and C. neoformans burden in the lung. Using gene-depleted mice, we show that reduction of eosinophilia and pathogen burden requires IL-12 and/or IFN-gamma. C. neoformans infection itself only partially induces OX40L expression by APCs. Provision of exogenous OX40L reveals a critical role of this pathway in the prevention of C. neoformans-induced eosinophilia. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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