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

Humphreys, Ian ORCID: https://orcid.org/0000-0002-9512-5337, Edwards, L CARDIFF??, Walzl, G, Rae, A. J, Dougan, G, Hill, S and Hussell, T 2003. OX40 ligation on activated T cells enhances the control of Cryptococcus neoformans and reduces pulmonary eosinophilia. Journal of Immunology 170 (12) , pp. 6125-6132. 10.4049/jimmunol.170.12.6125

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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

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	Adjuvants, Immunologic/administration & dosage;Adjuvants, Immunologic/biosynthesis;Adjuvants, Immunologic/metabolism*;Adjuvants, Immunologic/physiology;Animals;Antigens,Differentiation/administration & dosage;Antigens,Differentiation/metabolism;Bronchi/immunology;Bronchi/metabolism;Bronchi/microbiology;CD4-Positive T-Lymphocytes/immunology;CD4-Positive T-Lymphocytes/metabolism;CD4-Positive T-Lymphocytes/microbiology;Cryptococcus neoformans/growth & development;Cryptococcus neoformans/immunology*;Down-Regulation/immunology*;Eosinophils/immunology;Eosinophils/pathology;Female;Injections, Intraperitoneal;Interferon-gamma/biosynthesis;Interferon-gamma/deficiency;Interferon-gamma/genetics;Interferon-gamma/physiology;Ligands;Lung/immunology;Lung/metabolism;Lung/microbiology;Lymphocyte Activation/immunology*;Membrane Glycoproteins/administration & dosage;Membrane Glycoproteins/metabolism;Mice;Mice, Inbred C57BL;Mice, Knockout;Pulmonary Eosinophilia/genetics;Pulmonary Eosinophilia/microbiology;Pulmonary Eosinophilia/pathology;Pulmonary Eosinophilia/prevention & control*;Receptors, OX40;Receptors, Tumor Necrosis Factor*;Recombinant Fusion Proteins/administration & dosage;Recombinant Fusion Proteins/metabolism;T-Lymphocyte Subsets/immunology*;T-Lymphocyte Subsets/metabolism;T-Lymphocyte Subsets/microbiology*;Tumor Necrosis Factor Receptor Superfamily, Member 7/administration & dosage;Tumor Necrosis Factor Receptor Superfamily, Member 7/biosynthesis; Tumor Necrosis Factor Receptor Superfamily, Member;7/metabolism*;Tumor Necrosis Factors;
Publisher:	American Association of Immunologists
ISSN:	0022-1767
Date of Acceptance:	3 April 2003
Last Modified:	03 Nov 2022 10:10
URI:	https://orca.cardiff.ac.uk/id/eprint/107151

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