Title

Role of specific CD8+ T cells in the severity of a fulminant zoonotic viral hemorrhagic fever, hantavirus pulmonary syndrome

UMMS Affiliation

Center for Infectious Disease and Vaccine Research; Department of Pediatrics and Program in Molecular Medicine

Publication Date

2-24-2004

Document Type

Article

Subjects

Amino Acid Sequence; Animals; 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

Disciplines

Life Sciences | Medicine and Health Sciences

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.

Rights and Permissions

Citation: J Immunol. 2004 Mar 1;172(5):3297-304.

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Journal of immunology (Baltimore, Md. : 1950)

PubMed ID

14978138