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Blood, 1 November 2005, Vol. 106, No. 9, pp. 3166-3174.
Prepublished online as a Blood First Edition Paper on July 12, 2005; DOI 10.1182/blood-2005-01-0432.
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Submitted January 31, 2005
Accepted June 27, 2005
Loss of EBNA1-specific memory CD4+ and CD8+ T cells in HIV-infected patients progressing to AIDS-related non-Hodgkin Lymphoma
Erwan Piriou, Karel van Dort, Nening M Nanlohy, Marinus H van Oers, Frank Miedema, and Debbie van Baarle*
Department of Clinical Viro-Immunology, Sanquin Research at CLB and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Department of Clinical Viro-Immunology, Sanquin Research at CLB and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
Department of Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Department of Clinical Viro-Immunology, Sanquin Research at CLB and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
* Corresponding author; email: d.vanbaarle{at}azu.nl.
We previously observed a loss of EBV-specific CD8+ T-cell function in subjects progressing to EBV-related non-Hodgkin Lymphoma (NHL), correlating with loss of CD4+ T-cells. The aim of the present study was to determine the role of EBV-specific CD4+ T cells in the development of NHL during chronic HIV infection. To this end, CD4+ and CD8+ memory T cells, capable of proliferation and subsequent IFN production, directed against a latent (EBNA1) and a lytic (BZLF1) EBV antigen were studied longitudinally in 9 progressors to NHL, 4 progressors to non-EBV-related AIDS and 4 slow progressors to AIDS.
In all 3 groups, we observed a decline of EBV-specific memory CD4+ and CD8+ T-cell responses during HIV infection. However, whereas latent antigen EBNA1-specific CD4+ T cells were lost well before diagnosis in all subjects who developed an AIDS-related NHL (and EBNA1-specific CD8+ T cells were significantly lower compared to the other groups), these cells were better preserved in progressors to non-EBV-related disease and slow progressors. Loss of EBNA1-specific T-cell immunity thus might be important for progression to NHL. Interestingly, BZLF1-specific T cells were not lost in all progressors to NHL, suggesting a different function of these cells in the surveillance of EBV-infected B cells.
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