In conditions of T lymphopenia, interleukin (IL) 7 levels rise and, via T cell receptor for antigen–self–major histocompatibility complex (MHC) interaction, induce residual naive T cells to proliferate. This pattern of lymphopenia-induced “homeostatic” proliferation is typically quite slow and causes a gradual increase in total T cell numbers and differentiation into cells with features of memory cells. In contrast, we describe a novel form of homeostatic proliferation that occurs when naive T cells encounter raised levels of IL-2 and IL-15 in vivo. In this situation, CD8+ T cells undergo massive expansion and rapid differentiation into effector cells, thus closely resembling the T cell response to foreign antigens. However, the responses induced by IL-2/IL-15 are not seen in MHC-deficient hosts, implying that the responses are driven by self-ligands. Hence, homeostatic proliferation of naive T cells can be either slow or fast, with the quality of the response to self being dictated by the particular cytokine (IL-7 vs. IL-2/IL-15) concerned. The relevance of the data to the gradual transition of naive T cells into memory-phenotype (MP) cells with age is discussed.
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6 August 2007
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July 30 2007
An intense form of homeostatic proliferation of naive CD8+ cells driven by IL-2
Jae-Ho Cho,
Jae-Ho Cho
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
2Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia
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Onur Boyman,
Onur Boyman
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
3Division of Immunology and Allergy, University Hospital of Lausanne, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland
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Hee-Ok Kim,
Hee-Ok Kim
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
2Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia
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Bumsuk Hahm,
Bumsuk Hahm
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
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Mark P. Rubinstein,
Mark P. Rubinstein
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
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Chris Ramsey,
Chris Ramsey
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
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David M. Kim,
David M. Kim
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
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Charles D. Surh,
Charles D. Surh
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
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Jonathan Sprent
Jonathan Sprent
2Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia
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Jae-Ho Cho
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
2Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia
Onur Boyman
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
3Division of Immunology and Allergy, University Hospital of Lausanne, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland
Hee-Ok Kim
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
2Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia
Bumsuk Hahm
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
Mark P. Rubinstein
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
Chris Ramsey
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
David M. Kim
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
Charles D. Surh
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
Jonathan Sprent
2Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia
CORRESPONDENCE Jonathan Sprent: [email protected]
Abbreviations used: APC, allophycocyanin; γc, common γ chain; MP, memory phenotype; MHC-I−/−, Kb−/− Db−/− β2M−/−; SIYRp, SIYR peptide; Tg, transgenic.
Received:
April 12 2007
Accepted:
June 01 2007
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2007
J Exp Med (2007) 204 (8): 1787–1801.
Article history
Received:
April 12 2007
Accepted:
June 01 2007
Citation
Jae-Ho Cho, Onur Boyman, Hee-Ok Kim, Bumsuk Hahm, Mark P. Rubinstein, Chris Ramsey, David M. Kim, Charles D. Surh, Jonathan Sprent; An intense form of homeostatic proliferation of naive CD8+ cells driven by IL-2 . J Exp Med 6 August 2007; 204 (8): 1787–1801. doi: https://doi.org/10.1084/jem.20070740
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