Fas ligand is required for the development of respiratory syncytial virus vaccine-enhanced disease

Matthew R Olson; Steven M Varga

doi:10.4049/jimmunol.0803585

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Fas ligand is required for the development of respiratory syncytial virus vaccine-enhanced disease

Journal article

Peer reviewed

Fas ligand is required for the development of respiratory syncytial virus vaccine-enhanced disease

Matthew R Olson and Steven M Varga

The Journal of immunology (1950), Vol.182(5), pp.3024-3031

03/01/2009

DOI: 10.4049/jimmunol.0803585

PMCID: PMC2676854

PMID: 19234198

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Abstract

Children immunized with a formalin-inactivated respiratory syncytial virus (RSV) vaccine experienced enhanced disease and exhibited pulmonary eosinophilia upon natural RSV infection. BALB/c mice immunized with either formalin-inactivated RSV or a recombinant vaccinia virus (vacv) expressing the RSV attachment (G) protein develop extensive pulmonary eosinophilia after RSV challenge that mimics the eosinophilic response observed in the children during the 1960s vaccine trials. Fas ligand (FasL) is a major immune effector molecule that can contribute to the clearance of respiratory viruses. However, the role of FasL in the development of RSV vaccine-enhanced disease has not been elucidated. RSV challenge of vacvG-immunized gld mice, that lack functional FasL, results in diminished systemic disease as well as pulmonary eosinophilia. The magnitude of the secondary RSV G-specific CD4 T cell response was diminished in gld mice as compared with wild-type controls. Furthermore, we show that CD4 T cells isolated after RSV challenge of vacvG-immunized gld mice exhibit enhanced expression of Annexin V and caspase 3/7 indicating that FasL is important for either the survival or the expansion of virus-specific secondary effector CD4 T cells. Taken together, these data identify a previously undefined role for FasL in the accumulation of secondary effector CD4 T cells and the development of RSV vaccine-enhanced disease.

Respiratory Syncytial Virus Vaccines - immunology

Adjuvants, Immunologic - administration & dosage

CD8-Positive T-Lymphocytes - pathology

Humans

Pulmonary Eosinophilia - genetics

Respiratory Syncytial Viruses - immunology

CD4-Positive T-Lymphocytes - pathology

Lymphatic Diseases - genetics

Autoimmune Diseases - genetics

CD4-Positive T-Lymphocytes - immunology

Cell Differentiation - genetics

Immunization, Secondary

Mice, Mutant Strains

Epitopes, T-Lymphocyte - immunology

Fas Ligand Protein - biosynthesis

CD4-Positive T-Lymphocytes - virology

Autoimmune Diseases - pathology

Immunologic Memory - genetics

Pulmonary Eosinophilia - immunology

Adjuvants, Immunologic - physiology

Lymphatic Diseases - immunology

Autoimmune Diseases - immunology

Viral Envelope Proteins - administration & dosage

Pulmonary Eosinophilia - pathology

Fas Ligand Protein - physiology

Cell Differentiation - immunology

Animals

CD8-Positive T-Lymphocytes - virology

Respiratory Syncytial Virus Vaccines - administration & dosage

Lymphatic Diseases - pathology

Viral Envelope Proteins - immunology

Mice

Mice, Inbred BALB C

CD8-Positive T-Lymphocytes - immunology

Fas Ligand Protein - genetics

Details

Title: Subtitle: Fas ligand is required for the development of respiratory syncytial virus vaccine-enhanced disease
Creators: Matthew R Olson - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
Steven M Varga
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.182(5), pp.3024-3031
DOI: 10.4049/jimmunol.0803585
PMID: 19234198
PMCID: PMC2676854
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: R01 AI063520-02 / NIAID NIH HHS R01 AI063520 / NIAID NIH HHS AI 063520 / NIAID NIH HHS
Language: English
Date published: 03/01/2009
Academic Unit: Graduate College Admin and Gen; Microbiology and Immunology; Pathology
Record Identifier: 9984083870902771

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