IL-15 enhances CCR5-mediated migration of memory CD8+ T cells by upregulating CCR5 expression in the absence of TCR stimulation

In-Ho Seo; Hyuk Soo Eun; Ja Kyung Kim; Hoyoung Lee; Seongju Jeong; Seong Jin Choi; Jeewon Lee; Byung Seok Lee; Seok Hyun Kim; Woo Sun Rou; Dong Hyeon Lee; Won Kim; Su-Hyung Park; Eui-Cheol Shin

doi:10.1016/j.celrep.2021.109438

IL-15 enhances CCR5-mediated migration of memory CD8⁺ T cells by upregulating CCR5 expression in the absence of TCR stimulation

Cell Rep. 2021 Jul 27;36(4):109438. doi: 10.1016/j.celrep.2021.109438.

Authors

Affiliations

¹ Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
² Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea.
³ Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin 16995, Republic of Korea.
⁴ Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul 07061, Republic of Korea.
⁵ Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul 07061, Republic of Korea. Electronic address: [email protected].
⁶ Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea. Electronic address: [email protected].
⁷ Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea. Electronic address: [email protected].

PMID: 34320338
DOI: 10.1016/j.celrep.2021.109438

Abstract

During microbial infection, bystander CD8⁺ T cells that are not specific to infecting pathogens can be activated by interleukin (IL)-15. However, the tissue-homing properties of bystander-activated CD8⁺ T cells have not been elucidated. Here, we examine the effects of IL-15 on the expression of chemokine receptors on CD8⁺ T cells and their migration. IL-15 upregulates CCR5 in memory CD8⁺ T cells in the absence of T cell receptor (TCR) stimulation and enhances CCR5-dependent migration. IL-15-induced CCR5 upregulation is abrogated by TCR stimulation, indicating that CCR5 is upregulated in bystander-activated CD8⁺ T cells. Moreover, CCR5 signals increase proliferation and cytotoxic protein expression in IL-15-treated memory CD8⁺ T cells, although the increase has a small extent. CCR5 upregulation in bystander-activated CD8⁺ T cells is associated with severe liver injury in patients with acute hepatitis A. Altogether, the results indicate that CCR5 upregulation by IL-15 mediates the migration of bystander-activated CD8⁺ T cells.

Keywords: CCR5; IL-15; bystander-activated CD8(+) T cells; migration.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acute Disease
Adult
Animals
CD8-Positive T-Lymphocytes / metabolism*
Cell Death / genetics
Cell Movement*
Cell Proliferation / genetics
Female
Hepatitis A / complications
Hepatitis A / genetics
Hepatitis A / immunology
Humans
Immunologic Memory*
Inflammation / complications
Inflammation / immunology
Inflammation / pathology
Interleukin-15 / metabolism*
MAP Kinase Signaling System
Male
Mice
Mice, Inbred C57BL
Middle Aged
Receptors, Antigen, T-Cell / metabolism*
Receptors, CCR5 / genetics*
Receptors, CCR5 / metabolism
Receptors, CCR7 / metabolism
Up-Regulation / genetics
Young Adult

Substances

CCR7 protein, human
Interleukin-15
Receptors, Antigen, T-Cell
Receptors, CCR5
Receptors, CCR7