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Journal of Virology, July 2000, p. 6675-6679, Vol. 74, No. 14
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Functional Analysis of the CD4+ T-Cell Response to Epstein-Barr Virus: T-Cell-Mediated Activation of Resting B Cells and Induction of Viral BZLF1 Expression

Zheng Fudagger and Martin J. Cannon*

Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205

Received 18 January 2000/Accepted 26 April 2000

In contrast to the major role played by Epstein-Barr virus (EBV)-specific CD8+ cytotoxic T-cell responses in immunosurveillance, recent studies have offered the apparently paradoxical suggestion that development of EBV-driven human B-cell lymphoproliferative disorders and tumors in SCID/hu mice is dependent on the presence of T cells, in particular CD4+ T cells. This study presents a functional analysis of the CD4+ T-cell response to EBV and shows that while CD4+ T cells may be cytotoxic, they also express Th2 cytokines and CD40 ligand (gp39) and possess B-cell helper function. We show that EBV-specific CD4+ T cells can provide non-HLA-restricted help for activation of resting B cells via a gp39-CD40-dependent pathway and are able to induce expression of BZLF1, a viral lytic cycle transactivator in latently infected resting B cells, ultimately resulting in rapid outgrowth of transformed B-cell colonies. These results support the proposal that CD4+ T cells may play a key role in reactivation of latent EBV infection and may thus contribute to the pathogenesis of EBV-driven lymphoproliferative disorders.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Mail Slot 511, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205. Phone: (501) 296-1254. Fax: (501) 686-5359. E-mail: cannonmartin{at}exchange.uams.edu.

dagger Present address: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109.

Journal of Virology, July 2000, p. 6675-6679, Vol. 74, No. 14
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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