Strong HLA class I--restricted T cell responses in dengue hemorrhagic fever: a double-edged sword?

J Infect Dis. 2001 Dec 1;184(11):1369-73. doi: 10.1086/324320. Epub 2001 Nov 13.

Abstract

Dengue is an increasingly important cause of morbidity and mortality in the tropics, but vaccine development has been impeded by a poor understanding of disease pathogenesis and, in particular, of immunologic enhancement. In a large case-control study of Vietnamese patients with dengue hemorrhagic fever (DHF), variation at the HLA-A locus was significantly associated with susceptibility to DHF (P=.02), and specific HLA-A susceptibility and resistance alleles were identified. HLA-A-specific epitopes were predicted from binding motifs, and ELISPOT analyses of patients with DHF revealed high frequencies of circulating CD8 T lymphocytes that recognized both serotype-specific and -cross-reactive dengue virus epitopes. Thus, strong CD8 T cell responses are induced by natural dengue virus infection, and HLA class I genetic variation is a risk factor for DHF. These genetic and immunologic data support both protective and pathogenic roles for dengue virus-specific CD8 T cell responses in severe disease. The potentially pathogenic role of serotype-cross-reactive CD8 T cells poses yet another obstacle to successful dengue vaccine development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antigens, Viral / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Case-Control Studies
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Dengue Virus / immunology
  • Epitopes / immunology
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • HLA-A Antigens / genetics*
  • Humans
  • Interferon-gamma / biosynthesis
  • Lymphocyte Activation
  • Major Histocompatibility Complex
  • Male
  • Polymorphism, Genetic
  • Severe Dengue / genetics*
  • Severe Dengue / immunology*

Substances

  • Antigens, Viral
  • Epitopes
  • HLA-A Antigens
  • Interferon-gamma