High frequencies of functionally competent circulating Tax-specific CD8+ T cells in human T lymphotropic virus type 2 infection.
Human T lymphotropic virus type 2 (HTLV-2) is characterized by a clinically asymptomatic persistent infection in the vast majority of infected individuals. In this study, we have characterized for the first time ex vivo specific CTL responses against the HTLV-2 Tax protein. We could detect CTL responses only against a single HLA-A*0201-restricted Tax2 epitope, comprising residues 11-19 (LLYGYPVYV), among three alleles screened. Virus-specific CTLs could be detected in most evaluated subjects, with frequencies as high as 24% of circulating CD8(+) T cells. The frequency of specific CTLs had a statistically significant positive correlation with proviral load levels. The majority of virus-specific CD8(+) T cells exhibited an effector memory/terminally differentiated phenotype, expressed high levels of cytotoxicity mediators, including perforin and granzyme B, and lysed in vitro target cells pulsed with Tax2((11-19)) synthetic peptide in a dose-dependent manner. Our findings suggest that a strong, effective CTL response may control HTLV-2 viral burden and that this may be a significant factor in maintaining persistent infection and in the prevention of disease in infected individuals.
Oliveira
André L A
AL
Centre for Research in Infectious Diseases, University College Dublin, Dublin, Ireland.
Hayakawa
Hitoshi
H
Schor
Doris
D
Leite
Ana Claudia C B
AC
Espíndola
Otávio M
OM
Waters
Allison
A
Dean
Jonathan
J
Doherty
Derek G
DG
Araújo
Abelardo Q-C
AQ
Hall
William W
WW
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D003601:Cytotoxicity Tests, Immunologic; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D016356:Gene Products, tax / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen; D015491:HTLV-II Infections / Q000097:blood / Q000276:immunology* / Q000473:pathology; D015367:Human T-lymphotropic virus 2 / Q000276:immunology*; D006801:Humans; D018655:Lymphocyte Count; D011485:Protein Binding / Q000276:immunology; D011533:Proviruses / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000821:virology; D019562:Viral Load
D018984:Epitopes, T-Lymphocyte; D016356:Gene Products, tax; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; C514971:tax protein, Human T-lymphotrophic virus 2