KIR+CD8+ and NKG2A+CD8+ T cells are distinct innate-like populations in humans
Seong Jin Choi,
June-Young Koh,
Min-Seok Rha,
In-Ho Seo,
Hoyoung Lee,
Seongju Jeong,
Su-Hyung Park,
Eui-Cheol Shin
Affiliations
Seong Jin Choi
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; Department of Internal Medicine, Seoul National University Bundang Hospital, Gyeonggi-do 13620, Republic of Korea
June-Young Koh
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; Genome Insight, Inc., San Diego, La Jolla, CA, USA
Min-Seok Rha
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
In-Ho Seo
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
Hoyoung Lee
The Center for Viral Immunology, Korea Virus Research Institute, Institute for Basic Science (IBS), Daejeon 34126, Republic of Korea
Seongju Jeong
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
Su-Hyung Park
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; The Center for Epidemic Preparedness, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; Corresponding author
Eui-Cheol Shin
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; The Center for Viral Immunology, Korea Virus Research Institute, Institute for Basic Science (IBS), Daejeon 34126, Republic of Korea; Corresponding author
Summary: Subsets of the human CD8+ T cell population express inhibitory NK cell receptors, such as killer immunoglobulin-like receptors (KIRs) and NKG2A. In the present study, we examine the phenotypic and functional characteristics of KIR+CD8+ T cells and NKG2A+CD8+ T cells. KIRs and NKG2A tend to be expressed by human CD8+ T cells in a mutually exclusive manner. In addition, TCR clonotypes of KIR+CD8+ T cells barely overlap with those of NKG2A+CD8+ T cells, and KIR+CD8+ T cells are more terminally differentiated and replicative senescent than NKG2A+CD8+ T cells. Among cytokine receptors, IL12Rβ1, IL12Rβ2, and IL18Rβ are highly expressed by NKG2A+CD8+ T cells, whereas IL2Rβ is expressed by KIR+CD8+ T cells. IL-12/IL-18-induced production of IFN-γ is prominent in NKG2A+CD8+ T cells, whereas IL-15-induced NK-like cytotoxicity is prominent in KIR+CD8+ T cells. These findings suggest that KIR+CD8+ and NKG2A+CD8+ T cells are distinct innate-like populations with different cytokine responsiveness.