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Role of Specific CD8+ T Cells in the Severity of a Fulminant Zoonotic Viral Hemorrhagic Fever, Hantavirus Pulmonary Syndrome
- Source :
- The Journal of Immunology. 172:3297-3304
- Publication Year :
- 2004
- Publisher :
- The American Association of Immunologists, 2004.
-
Abstract
- We report on the role of specific CD8+ T cells in the pathogenesis of a highly lethal human viral disease, hantavirus pulmonary syndrome (HPS). HPS is a zoonotic disease caused by transmission of Sin Nombre virus (SNV) from chronically infected deer mice. In humans, this fulminant infection is characterized by lung capillary leakage, respiratory failure, and cardiogenic shock. Individuals with HLA-B*3501 have an increased risk of developing severe HPS, suggesting that CD8+ T cell responses to SNV contribute to pathogenesis. We identified three CD8+ T cell epitopes in SNV presented by HLA-B*3501 and quantitated circulating SNV-specific CD8+ T cells in 11 acute HPS patients using HLA/peptide tetramers. We found significantly higher frequencies of SNV-specific T cells in patients with severe HPS requiring mechanical ventilation (up to 44.2% of CD8+ T cells) than in moderately ill HPS patients hospitalized but not requiring mechanical ventilation (up to 9.8% of CD8+ T cells). These results imply that virus-specific CD8+ T cells contribute to HPS disease outcome. Intense CD8+ T cell responses to SNV may be induced by the encounter of the unnatural human host to this zoonotic virus without coevolution. This may also be the immunopathologic basis of other life-threatening human virus infections.
- Subjects :
- Hemorrhagic Fevers, Viral
Sin Nombre virus
viruses
T cell
Fulminant
Molecular Sequence Data
Immunology
Epitopes, T-Lymphocyte
Human leukocyte antigen
CD8-Positive T-Lymphocytes
Hantavirus Pulmonary Syndrome
Biology
Severity of Illness Index
Zoonoses
medicine
Animals
Humans
Immunology and Allergy
Cytotoxic T cell
Amino Acid Sequence
Lymphocyte Count
Hantavirus pulmonary syndrome
Virology
Kinetics
medicine.anatomical_structure
Leukocytes, Mononuclear
Viral disease
CD8
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 172
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....cf112bdf9dc02de045237b11f4347713