Role of specific CD8+ T cells in the severity of a fulminant zoonotic viral hemorrhagic fever, hantavirus pulmonary syndrome
Authors
Kilpatrick, Elizabeth D.Terajima, Masanori
Koster, Frederick T.
Catalina, Michelle D.
Cruz, John
Ennis, Francis A.
UMass Chan Affiliations
Department of Pediatrics and Program in Molecular MedicineCenter for Infectious Disease and Vaccine Research
Document Type
Journal ArticlePublication Date
2004-02-24Keywords
Amino Acid SequenceAnimals
CD8-Positive T-Lymphocytes
Epitopes, T-Lymphocyte
Hantavirus Pulmonary Syndrome
Hemorrhagic Fevers, Viral
Humans
Kinetics
Leukocytes, Mononuclear
Lymphocyte Count
Molecular Sequence Data
Severity of Illness Index
Sin Nombre virus
Zoonoses
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
J Immunol. 2004 Mar 1;172(5):3297-304.
DOI
10.4049/jimmunol.172.5.3297Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38228PubMed ID
14978138Related Resources
ae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.172.5.3297