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PMID: 18689546 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

IL-7 and IL-15 differentially regulate CD8+ T-cell subsets during contraction of the immune response.

Blood ·Vol. 112 ·No. 9 ·2008-11-01 ·Pages 3704-12

Rubinstein MP, Lind NA, Purton JF, Filippou P, Best JA, McGhee PA, Surh CD, Goldrath AW

Abstract

Although it is known that interleukin-7 (IL-7) and IL-15 influence the survival and turnover of CD8+ T cells, less is known about how these cytokines affect different subsets during the course of the immune response. We find that IL-7 and IL-15 differentially regulate CD8+ T-cell subsets defined by KLRG1 and CD127 expression during the contraction phase of the immune response. The provision of IL-15, or the related cytokine IL-2, during contraction led to the preferential accumulation of KLRG1(hi)CD127(lo) CD8+ T cells, whereas provision of IL-7 instead favored the accumulation of KLRG1(lo)CD127(hi) cells. While IL-7 and IL-15 both induced proliferation of KLRG1(lo) cells, KLRG1(hi) cells exhibited an extraordinarily high level of resistance to cytokine-driven proliferation in vivo despite their dramatic accumulation upon IL-15 administration. These results suggest that IL-15 and IL-2 greatly improve the survival of KLRG1(hi) CD8+ T cells, which are usually destined to perish during contraction, without inducing proliferation. As the availability of IL-15 and IL-2 is enhanced during periods of extended inflammation, our results suggest a mechanism in which a population of cytokine-dependent KLRG1(hi) CD8+ T cells is temporarily retained for improved immunity. Consideration of these findings may aid in the development of immunotherapeutic strategies against infectious disease and cancer.

MeSH Terms
Adoptive Transfer Animals CD8-Positive T-Lymphocytes/cytology,drug effects,immunology Cell Proliferation/drug effects Cell Survival/drug effects Humans Interleukin-15/metabolism,pharmacology Interleukin-7/metabolism,pharmacology Mice Mice, Inbred C57BL Mice, Knockout Ovalbumin/immunology Receptors, Interleukin-15/metabolism Receptors, Interleukin-2/metabolism Recombinant Proteins/pharmacology T-Lymphocyte Subsets/cytology,drug effects,immunology
Chemicals
Interleukin-15 Interleukin-7 Receptors, Interleukin-15 Receptors, Interleukin-2 Recombinant Proteins Ovalbumin
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Rubinstein Mark P
Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0377, USA.
Lind Nicholas A
Purton Jared F
Filippou Pauline
Best J Adam
McGhee Patrick A
Surh Charles D
Goldrath Ananda W
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
1528-0020
DOI
10.1182/blood-2008-06-160945
Published
2008-11-01
Epub
2008-00-08
Pages
3704-12
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC2572798
Subset
IM
Grants
NIAID NIH HHS · R01 AI067545 · United States
NIAID NIH HHS · T32 AI060536 · United States
NIAID NIH HHS · R01AI67545 · United States
NIAID NIH HHS · T32AI060536-02 · United States
External Links
PubMed source DOI: 10.1182/blood-2008-06-160945 PMC Full Text View journal details
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