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
Affiliations
In-Ho Seo
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
Hyuk Soo Eun
Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea
Ja Kyung Kim
Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin 16995, Republic of Korea
Hoyoung Lee
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
Seongju Jeong
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
Seong Jin Choi
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
Jeewon Lee
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
Byung Seok Lee
Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea
Seok Hyun Kim
Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea
Woo Sun Rou
Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea
Dong Hyeon Lee
Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul 07061, Republic of Korea
Won Kim
Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul 07061, Republic of Korea; Corresponding author
Su-Hyung Park
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea; Corresponding author
Eui-Cheol Shin
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea; Corresponding author
Summary: 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.
