T cell responses in dengue hemorrhagic fever: are cross-reactive T cells suboptimal?
Dengue virus infection poses a growing public health and economic burden in a number of tropical and subtropical countries. Dengue circulates as a number of quasispecies, which can be divided by serology into four groups or serotypes. An interesting feature of Dengue, recognized over five decades ago, is that most severe cases that show hemorrhagic fever are not suffering from a primary infection. Instead, they are reinfected with a virus of different serotype. This observation poses considerable problems in vaccine design, and it is therefore imperative to gain a full understanding of the mechanisms underlying this immunological enhancement of disease. In this study, we examined a T cell epitope restricted by HLA-A*24, a major MHC class I allele, in Southeast Asia in a cohort of children admitted to a hospital with acute Dengue infection. The cytokine profiles and the degranulation capacity of T cells generated to this epitope are defined and compared across different viral serotypes. Cross-reactive Dengue-specific T cells seem to show suboptimal degranulation but high cytokine production, which may contribute to the development of the vascular leak characteristic of Dengue hemorrhagic fever.
Mongkolsapaya
Juthathip
J
Department of Immunology, Division of Medicine, Hammersmith Hospital, Imperial College, Du Cane Road, London W12 0NN, United Kingdom.
Duangchinda
Thaneeya
T
Dejnirattisai
Wanwisa
W
Vasanawathana
Sirijit
S
Avirutnan
Panisadee
P
Jairungsri
Aroonroong
A
Khemnu
Nuanpan
N
Tangthawornchaikul
Nattaya
N
Chotiyarnwong
Pojchong
P
Sae-Jang
Kanokwan
K
Koch
Michael
M
Jones
Yvonne
Y
McMichael
Andrew
A
Xu
Xiaoning
X
Malasit
Prida
P
Screaton
Gavin
G
D000595:Amino Acid Sequence; D002478:Cells, Cultured; D003429:Cross Reactions / Q000276:immunology; D003716:Dengue Virus / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D015788:HLA-A1 Antigen / Q000737:chemistry / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D008958:Models, Molecular; D010641:Phenotype; D020836:Protein Structure, Quaternary; D019595:Severe Dengue / Q000276:immunology* / Q000821:virology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D015788:HLA-A1 Antigen; D015789:HLA-A2 Antigen