Loss of EBNA1-specific memory CD4+ and CD8+ T cells in HIV-infected patients progressing to AIDS-related non-Hodgkin lymphoma.
We previously observed a loss of Epstein-Barr virus (EBV)-specific CD8+ T cells 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 both proliferation and subsequent interferon gamma (IFNgamma) production, directed against a latent (Epstein-Barr virus nuclear antigen 1 [EBNA1]) and a lytic (BamH fragment Z left frame 1 [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 with 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.
Piriou
Erwan
E
Department of Clinical Viro-Immunology, Sanquin Research at CLB and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands.
van Dort
Karel
K
Nanlohy
Nening M
NM
van Oers
Marinus H J
MH
Miedema
Frank
F
van Baarle
Debbie
D
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000276:immunology / Q000821:virology; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D018450:Disease Progression; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007700:Kinetics; D016483:Lymphoma, AIDS-Related / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008228:Lymphoma, Non-Hodgkin / Q000150:complications* / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008875:Middle Aged
D019309:Epstein-Barr Virus Nuclear Antigens; C417029:EBV-encoded nuclear antigen 1