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Journal of Virology, April 2001, p. 3740-3752, Vol. 75, No. 8
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.8.3740-3752.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

CD4+ T-Cell Effectors Inhibit Epstein-Barr Virus-Induced B-Cell Proliferation

Sarah Nikiforow,1 Kim Bottomly,1 and George Miller2,*

Departments of Immunobiology1 and Pediatrics, Epidemiology & Public Health, Molecular Biophysics, and Biochemistry,2 Yale University School of Medicine, New Haven, Connecticut 06520

Received 4 October 2000/Accepted 16 January 2001

In immunodeficient hosts, Epstein-Barr virus (EBV) often induces extensive B-cell lymphoproliferative disease and lymphoma. Without effective in vitro immune surveillance, B cells infected by the virus readily form immortalized cell lines. In the regression assay, memory T cells inhibit the formation of foci of EBV-transformed B cells that follows recent in vitro infection by EBV. No one has yet addressed which T cell regulates the early proliferative phase of B cells newly infected by EBV. Using new quantitative methods, we analyzed T-cell surveillance of EBV-mediated B-cell proliferation. We found that CD4+ T cells play a significant role in limiting proliferation of newly infected, activated CD23+ B cells. In the absence of T cells, EBV-infected CD23+ B cells divided rapidly during the first 3 weeks after infection. Removal of CD4+ but not CD8+ T cells also abrogated immune control. Purified CD4+ T cells eliminated outgrowth when added to EBV-infected B cells. Thus, unlike the killing of EBV-infected lymphoblastoid cell lines, in which CD8+ cytolytic T cells play an essential role, prevention of early-phase EBV-induced B-cell proliferation requires CD4+ effector T cells.

* Corresponding author. Mailing address: Department of Pediatrics, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06520. Phone: (203) 785-4758. Fax: (203) 785-6961. E-mail: george.miller{at}yale.edu.

Journal of Virology, April 2001, p. 3740-3752, Vol. 75, No. 8
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.8.3740-3752.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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