OX40 ligation on activated T cells enhances the control of Cryptococcus neoformans and reduces pulmonary eosinophilia.

Abstract

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.

• Authors: Ian R Humphreys, Lorna Edwards, Gerhard Walzl, Aaron J Rae, Gordon Dougan, Sue Hill, Tracy Hussell
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 170 Issue 12 Pg. 6125-32 (Jun 15 2003) ISSN: 0022-1767 [Print] United States
• PMID: 12794142 (Publication Type: Journal Article)

Chemical References

• Adjuvants, Immunologic
• Antigens, Differentiation
• Ligands
• Membrane Glycoproteins
• OX40 Ligand
• OX40Ig
• Receptors, OX40
• Receptors, Tumor Necrosis Factor
• Recombinant Fusion Proteins
• Tnfrsf4 protein, mouse
• Tnfsf4 protein, mouse
• Tumor Necrosis Factor Receptor Superfamily, Member 7
• Tumor Necrosis Factors
• Interferon-gamma

Topics

• Adjuvants, Immunologic (administration & dosage, biosynthesis, metabolism, physiology)
• Animals
• Antigens, Differentiation (administration & dosage, metabolism)
• Bronchi (immunology, metabolism, microbiology)
• CD4-Positive T-Lymphocytes (immunology, metabolism, microbiology)
• Cryptococcus neoformans (growth & development, immunology)
• Down-Regulation (immunology)
• Eosinophils (immunology, pathology)
• Female
• Injections, Intraperitoneal
• Interferon-gamma (biosynthesis, deficiency, genetics, physiology)
• Ligands
• Lung (immunology, metabolism, microbiology)
• Lymphocyte Activation (immunology)
• Membrane Glycoproteins (administration & dosage, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• OX40 Ligand
• Pulmonary Eosinophilia (genetics, microbiology, pathology, prevention & control)
• Receptors, OX40
• Receptors, Tumor Necrosis Factor
• Recombinant Fusion Proteins (administration & dosage, metabolism)
• T-Lymphocyte Subsets (immunology, metabolism, microbiology)
• Tumor Necrosis Factor Receptor Superfamily, Member 7 (administration & dosage, biosynthesis, metabolism)
• Tumor Necrosis Factors