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Journal of Virology, October 2004, p. 10953-10959, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.10953-10959.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Enhanced Expression of Cell Cycle Regulatory Genes in Virus-Specific Memory CD8+ T Cells

Donald R. Latner, Susan M. Kaech,{dagger} and Rafi Ahmed*

Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia

Received 4 April 2004/ Accepted 15 June 2004

Unlike naive CD8+ T cells, antigen-experienced memory CD8+ T cells persist over time due to their unique ability to homeostatically proliferate. It was hypothesized that memory cells might differentially regulate the expression of genes that control the cell cycle to facilitate homeostatic proliferation. To test this, the expression levels of 96 different cell cycle regulatory genes were compared between transgenic naive and memory CD8+ T cells that specifically recognize the GP33-41 epitope of lymphocytic choriomeningitis virus (LCMV). It was discovered that relative to naive cells, memory cells overexpress several important genes that control the transition between G1 and S phase. Some of these genes include those encoding cyclins D3, D2, B1, C, and H, cyclin-dependent kinases (cdk's) 4 and 6, the cdk inhibitors p16, p15, and p18, and other genes involved in protein degradation and DNA replication. Importantly, these differences were observed both in total populations of LCMV-specific naive and memory CD8+ cells and in LCMV-specific CD8+ T-cell populations that were in the G1 phase of the cell cycle only. In addition, the expression differences between naive and memory cells were exaggerated following antigenic stimulation. The fact that memory cells are precharged with several of the major factors that are necessary for the G1- to-S-phase transition suggests they may require a lower threshold of stimulation to enter the cell cycle.

* Corresponding author. Mailing address: Emory Vaccine Center, 1510 Clifton Rd., G211, Atlanta, GA 30322. Phone: (404) 727-9301. Fax: (404) 727-3722. E-mail: ra{at}microbio.emory.edu.

{dagger} Present address: Section of Immunology, Yale Medical School, New Haven, CT 06520.

Journal of Virology, October 2004, p. 10953-10959, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.10953-10959.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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