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Journal of Virology, June 2009, p. 6192-6198, Vol. 83, No. 12
0022-538X/09/$08.00+0     doi:10.1128/JVI.00239-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Acquisition of Polyfunctionality by Epstein-Barr Virus-Specific CD8+ T Cells Correlates with Increased Resistance to Galectin-1-Mediated Suppression{triangledown}

Corey Smith, Leone Beagley, and Rajiv Khanna*

Australian Centre for Vaccine Development and Tumour Immunology Laboratory, Division of Immunology, Queensland Institute of Medical Research, Brisbane, Australia 4029

Received 3 February 2009/ Accepted 31 March 2009

Latent membrane antigen 1 and -2 (LMP-1/2)-specific CD8+ T cells from newly diagnosed and relapsed Hodgkin's lymphoma (HL) patients display a selective functional impairment. In contrast, CD8+ T cells specific for Epstein-Barr virus (EBV) nuclear proteins and lytic antigens retain normal T-cell function. Reversion to a dysfunctional phenotype of LMP-1/2-specific T cells is coincident with the regression of HL. To delineate the potential basis for this differential susceptibility for the loss of function, we have carried out a comprehensive functional analysis of EBV-specific T cells using ex vivo multiparametric flow cytometry in combination with assessment of antigen-driven proliferative potential. This analysis revealed that LMP-1/2-specific T cells from healthy virus carriers display a deficient polyfunctional profile compared to that of T cells specific for epitopes derived from EBV nuclear proteins and lytic antigens. Furthermore, LMP-specific T-cells are highly susceptible to galectin-1-mediated immunosuppression and are less likely to degranulate following exposure to cognate peptide epitopes and poorly recognized endogenously processed epitopes from virus-infected B cells. More importantly, ex vivo stimulation of these T cells with an adenoviral vector encoding multiple minimal CD8+ T-cell epitopes as a polyepitope, in combination with a {gamma}C cytokine, interleukin-2, restored polyfunctionality and shielded these cells from the inhibitory effects of galectin-1.

* Corresponding author. Mailing address: Division of Infectious Diseases and Immunology, CBCRC Building, Queensland Institute of Medical Research, 300 Herston Rd, Brisbane, Australia 4029. Phone: 61-7-3362 0385. Fax: 61-7-3845 3510. E-mail: rajiv.Khanna{at}qimr.edu.au

{triangledown} Published ahead of print on 8 April 2009.

Journal of Virology, June 2009, p. 6192-6198, Vol. 83, No. 12
0022-538X/09/$08.00+0     doi:10.1128/JVI.00239-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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