HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0900508v1 183/5/2957    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Oliveira, A. L. A. Articles by Hall, W. W. PubMed PubMed Citation Articles by Oliveira, A. L. A. Articles by Hall, W. W.

High Frequencies of Functionally Competent Circulating Tax-Specific CD8⁺ T Cells in Human T Lymphotropic Virus Type 2 Infection

André L. A. Oliveira^*, Hitoshi Hayakawa^*, Doris Schor, Ana Claudia C. B. Leite, Otávio M. Espíndola, Allison Waters, Jonathan Dean^*, Derek G. Doherty^¶,||, Abelardo Q.-C. Araújo^*, and William W. Hall^1,*,

^* Centre for Research in Infectious Diseases and National Virus Reference Laboratory, University College Dublin, Dublin, Ireland; Viral Pathogenesis Research Laboratory and Laboratory for Research in Neuroinfections, Evandro Chagas Institute for Clinical Research, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; ^¶ Cellular Immunology Laboratory, Department of Biology, National University of Ireland, Maynooth, Ireland; and ^|| Department of Immunology, Trinity College Dublin, St. James’s Hospital, Dublin, Ireland

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Address correspondence and reprint requests to Prof. W. Hall, The Centre for Research in Infectious Diseases, University College Dublin, Belfield, Dublin 4, Ireland. E-mail address: william.hall{at}ucd.ie

² Abbreviations used in this paper: HTLV, human T lymphotropic virus; ATLL, adult T cell leukemia/lymphoma; HAM/TSP, HTLV-1-associated myelopathy/tropical spastic paraparesis; PD-1, programmed death 1; PVL, proviral load; T_CM, central memory T cell; T_EM, effector memory T cell; T_EMRA, terminally differentiated memory T cell; T_N, naive T cell.