Evidence of a novel IL-2/15Rβ-targeted cytokine involved in homeostatic proliferation of memory CD8+ T cells

Daisuke Kamimura, Naoko Ueda, Yukihisa Sawa, Shinji Hachida, Toru Atsumi, Takayuki Nakagawa, Shinichiro Sawa, Gui Hua Jin, Haruhiko Suzuki, Katsuhiko Ishihara, Masaaki Murakami, Toshio Hirano

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The homeostasis of memory CD8+ T cells is regulated by cytokines. IL-15 is shown to promote the proliferation of Memory CD8+ T cells, while IL-2 suppresses their division in vivo. This inhibitory efect of IL-2 appears to occur indirectly, through other cell populations including CD25+CD4+ T cells; however, the details of this mechanism remain unclear. In this study, we show that 1) both Ag-experienced and memory phenotype CD8+ T cells divided after the depletion of IL-2 in vivo; 2) this division occurred normally and CD44highIL-2/ 15Rβhigh CD8+ T cells generated after IL-2 depletion in IL-15 knockout (KO) and in IL-7-depleted IL-15 KO mice; 3) surprisingly, the blockade of IL-2/15Rβ signaling in IL-2-depleted IL-15 KO mice completely abolished the division of memory CD8+ T cells, although the only cytokines known to act through IL-2/15Rβ are IL-2 and IL-15; and 4) the expression of IL-2/15Rβ molecules on memory CD8+ T cells was required for their division induced by IL-2 depletion. These results demonstrate that the depletion of IL-2 in vivo induced memory CD8+ T cell division by an IL-15-independent but by an IL-2/15Rβ-dependent mechanism, suggesting the existence of a novel IL-2/15Rβ-utilizing cytokine that acts directly on memory CD8+ T cells to promote cell division.

Original languageEnglish
Pages (from-to)6041-6049
Number of pages9
JournalJournal of Immunology
Volume173
Issue number10
Publication statusPublished - Nov 15 2004
Externally publishedYes

Fingerprint

Interleukin-2
Cytokines
T-Lymphocytes
Interleukin-15
Knockout Mice
Cell Division
Interleukin-7
Interleukin-4
Homeostasis
Phenotype

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Kamimura, D., Ueda, N., Sawa, Y., Hachida, S., Atsumi, T., Nakagawa, T., ... Hirano, T. (2004). Evidence of a novel IL-2/15Rβ-targeted cytokine involved in homeostatic proliferation of memory CD8+ T cells. Journal of Immunology, 173(10), 6041-6049.

Evidence of a novel IL-2/15Rβ-targeted cytokine involved in homeostatic proliferation of memory CD8+ T cells. / Kamimura, Daisuke; Ueda, Naoko; Sawa, Yukihisa; Hachida, Shinji; Atsumi, Toru; Nakagawa, Takayuki; Sawa, Shinichiro; Jin, Gui Hua; Suzuki, Haruhiko; Ishihara, Katsuhiko; Murakami, Masaaki; Hirano, Toshio.

In: Journal of Immunology, Vol. 173, No. 10, 15.11.2004, p. 6041-6049.

Research output: Contribution to journalArticle

Kamimura, D, Ueda, N, Sawa, Y, Hachida, S, Atsumi, T, Nakagawa, T, Sawa, S, Jin, GH, Suzuki, H, Ishihara, K, Murakami, M & Hirano, T 2004, 'Evidence of a novel IL-2/15Rβ-targeted cytokine involved in homeostatic proliferation of memory CD8+ T cells', Journal of Immunology, vol. 173, no. 10, pp. 6041-6049.
Kamimura D, Ueda N, Sawa Y, Hachida S, Atsumi T, Nakagawa T et al. Evidence of a novel IL-2/15Rβ-targeted cytokine involved in homeostatic proliferation of memory CD8+ T cells. Journal of Immunology. 2004 Nov 15;173(10):6041-6049.
Kamimura, Daisuke ; Ueda, Naoko ; Sawa, Yukihisa ; Hachida, Shinji ; Atsumi, Toru ; Nakagawa, Takayuki ; Sawa, Shinichiro ; Jin, Gui Hua ; Suzuki, Haruhiko ; Ishihara, Katsuhiko ; Murakami, Masaaki ; Hirano, Toshio. / Evidence of a novel IL-2/15Rβ-targeted cytokine involved in homeostatic proliferation of memory CD8+ T cells. In: Journal of Immunology. 2004 ; Vol. 173, No. 10. pp. 6041-6049.
@article{4f9e76682ada4b38ac3751c5441af4dc,
title = "Evidence of a novel IL-2/15Rβ-targeted cytokine involved in homeostatic proliferation of memory CD8+ T cells",
abstract = "The homeostasis of memory CD8+ T cells is regulated by cytokines. IL-15 is shown to promote the proliferation of Memory CD8+ T cells, while IL-2 suppresses their division in vivo. This inhibitory efect of IL-2 appears to occur indirectly, through other cell populations including CD25+CD4+ T cells; however, the details of this mechanism remain unclear. In this study, we show that 1) both Ag-experienced and memory phenotype CD8+ T cells divided after the depletion of IL-2 in vivo; 2) this division occurred normally and CD44highIL-2/ 15Rβhigh CD8+ T cells generated after IL-2 depletion in IL-15 knockout (KO) and in IL-7-depleted IL-15 KO mice; 3) surprisingly, the blockade of IL-2/15Rβ signaling in IL-2-depleted IL-15 KO mice completely abolished the division of memory CD8+ T cells, although the only cytokines known to act through IL-2/15Rβ are IL-2 and IL-15; and 4) the expression of IL-2/15Rβ molecules on memory CD8+ T cells was required for their division induced by IL-2 depletion. These results demonstrate that the depletion of IL-2 in vivo induced memory CD8+ T cell division by an IL-15-independent but by an IL-2/15Rβ-dependent mechanism, suggesting the existence of a novel IL-2/15Rβ-utilizing cytokine that acts directly on memory CD8+ T cells to promote cell division.",
author = "Daisuke Kamimura and Naoko Ueda and Yukihisa Sawa and Shinji Hachida and Toru Atsumi and Takayuki Nakagawa and Shinichiro Sawa and Jin, {Gui Hua} and Haruhiko Suzuki and Katsuhiko Ishihara and Masaaki Murakami and Toshio Hirano",
year = "2004",
month = "11",
day = "15",
language = "English",
volume = "173",
pages = "6041--6049",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "10",

}

TY - JOUR

T1 - Evidence of a novel IL-2/15Rβ-targeted cytokine involved in homeostatic proliferation of memory CD8+ T cells

AU - Kamimura, Daisuke

AU - Ueda, Naoko

AU - Sawa, Yukihisa

AU - Hachida, Shinji

AU - Atsumi, Toru

AU - Nakagawa, Takayuki

AU - Sawa, Shinichiro

AU - Jin, Gui Hua

AU - Suzuki, Haruhiko

AU - Ishihara, Katsuhiko

AU - Murakami, Masaaki

AU - Hirano, Toshio

PY - 2004/11/15

Y1 - 2004/11/15

N2 - The homeostasis of memory CD8+ T cells is regulated by cytokines. IL-15 is shown to promote the proliferation of Memory CD8+ T cells, while IL-2 suppresses their division in vivo. This inhibitory efect of IL-2 appears to occur indirectly, through other cell populations including CD25+CD4+ T cells; however, the details of this mechanism remain unclear. In this study, we show that 1) both Ag-experienced and memory phenotype CD8+ T cells divided after the depletion of IL-2 in vivo; 2) this division occurred normally and CD44highIL-2/ 15Rβhigh CD8+ T cells generated after IL-2 depletion in IL-15 knockout (KO) and in IL-7-depleted IL-15 KO mice; 3) surprisingly, the blockade of IL-2/15Rβ signaling in IL-2-depleted IL-15 KO mice completely abolished the division of memory CD8+ T cells, although the only cytokines known to act through IL-2/15Rβ are IL-2 and IL-15; and 4) the expression of IL-2/15Rβ molecules on memory CD8+ T cells was required for their division induced by IL-2 depletion. These results demonstrate that the depletion of IL-2 in vivo induced memory CD8+ T cell division by an IL-15-independent but by an IL-2/15Rβ-dependent mechanism, suggesting the existence of a novel IL-2/15Rβ-utilizing cytokine that acts directly on memory CD8+ T cells to promote cell division.

AB - The homeostasis of memory CD8+ T cells is regulated by cytokines. IL-15 is shown to promote the proliferation of Memory CD8+ T cells, while IL-2 suppresses their division in vivo. This inhibitory efect of IL-2 appears to occur indirectly, through other cell populations including CD25+CD4+ T cells; however, the details of this mechanism remain unclear. In this study, we show that 1) both Ag-experienced and memory phenotype CD8+ T cells divided after the depletion of IL-2 in vivo; 2) this division occurred normally and CD44highIL-2/ 15Rβhigh CD8+ T cells generated after IL-2 depletion in IL-15 knockout (KO) and in IL-7-depleted IL-15 KO mice; 3) surprisingly, the blockade of IL-2/15Rβ signaling in IL-2-depleted IL-15 KO mice completely abolished the division of memory CD8+ T cells, although the only cytokines known to act through IL-2/15Rβ are IL-2 and IL-15; and 4) the expression of IL-2/15Rβ molecules on memory CD8+ T cells was required for their division induced by IL-2 depletion. These results demonstrate that the depletion of IL-2 in vivo induced memory CD8+ T cell division by an IL-15-independent but by an IL-2/15Rβ-dependent mechanism, suggesting the existence of a novel IL-2/15Rβ-utilizing cytokine that acts directly on memory CD8+ T cells to promote cell division.

UR - http://www.scopus.com/inward/record.url?scp=8444225681&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=8444225681&partnerID=8YFLogxK

M3 - Article

C2 - 15528339

AN - SCOPUS:8444225681

VL - 173

SP - 6041

EP - 6049

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 10

ER -