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Journal of Virology, September 2004, p. 9740-9749, Vol. 78, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.18.9740-9749.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Recombinant Interleukin-7 Induces Proliferation of Naive Macaque CD4+ and CD8+ T Cells In Vivo

Marcin Moniuszko,1,{dagger} Terry Fry,2 Wen-Po Tsai,1 Michel Morre,3 Brigitte Assouline,3 Pierre Cortez,3 Mark G. Lewis,4 Scott Cairns,5 Crystal Mackall,2 and Genoveffa Franchini1*

Animal Models and Retroviral Vaccines Section,1 Immunology Section, Pediatric Oncology Branch, National Cancer Institute,2 Henry Jackson Foundation, Bethesda,5 Bioqual, Rockville, Maryland,4 Cytheris, Vanves, France3

Received 26 March 2004/ Accepted 17 May 2004

Interleukin-7 (IL-7) regulates T-cell homeostasis, and its availability is augmented in lymphopenic hosts. Naive CD8+ T cells transferred to lymphopenic mice acquire a memory-like phenotype, raising the possibility that IL-7 is the biological mediator of this effect. Here, we provide direct evidence that IL-7 induces the acquisition of memory-cell markers not only in CD8+ T cells but also in CD4+ T-cell subsets in immune-competent Indian rhesus macaques. The increase of these memory-like populations was dependent on the dose of the cytokine, and these cells were found in the blood as well as secondary lymphoid organs. Memory-like CD4+ and CD8+ T cells acquired the ability to secrete tumor necrosis factor alpha and, to a lesser extent, gamma interferon following stimulation with a cognate antigen. The phenotypic change observed in naive T cells was promptly reversed after discontinuation of IL-7. Importantly, IL-7 induced cycling of both CD4+ and CD8+ central memory and effector memory T cells, demonstrating its contribution to the maintenance of the entire T-cell pool. Thus, IL-7 may be of benefit in the treatment of iatrogenic or virus-induced T-cell depletion.

* Corresponding author. Mailing address: National Cancer Institute, Bldg. 41, Rm. D804, Bethesda, MD 20892-5065. Phone: (301) 496-2386. Fax: (301) 402-0055. E-mail: franchig{at}mail.nih.gov.

{dagger} Present address: Department of Allergology and Internal Diseases, Medical University of Bialystok, 15-276 Bialystok, Poland.

Journal of Virology, September 2004, p. 9740-9749, Vol. 78, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.18.9740-9749.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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