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Int J Infect Dis. 2020;97:313-321.

Aberrant hyperactivation of cytotoxic T-cell as a potential determinant of COVID-19 severity.

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제1저자 강창경, 한기찬, 김민지 · 교신저자 김항래, 오명돈

PMID 32492530 PMC7261468 DOI 10.1016/j.ijid.2020.05.106 IF 4.6 감염내과
소속 (6)
  1. Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
  2. Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Department of Anatomy & Cell Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; BK21 Plus Biomedical Science Project, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
  3. Wide River Institute of Immunology, Seoul National University, Hongcheon 25159, Republic of Korea.
  4. Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea.
  5. Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Department of Anatomy & Cell Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; BK21 Plus Biomedical Science Project, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Wide River Institute of Immunology, Seoul National University, Hongcheon 25159, Republic of Korea; Medical Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea. Electronic address: hangrae2@snu.ac.kr.
  6. Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea. Electronic address: mdohmd@snu.ac.kr.

Abstract

OBJECTIVES We hypothesized that immune response may contribute to progression of coronavirus disease-19 (COVID-19) at the second week of illness. Therefore, we compared cell-mediated immune (CMI) responses between severe and mild COVID-19 cases.

METHODS We examined peripheral blood mononuclear cells of laboratory-confirmed COVID-19 patients from their first and third weeks of illness. Severe pneumonia was defined as an oxygen saturation ≤93% at room air. Expressions of molecules related to T-cell activation and functions were analyzed by flow cytometry.

RESULTS The population dynamics of T cells at the first week were not different between the two groups. However, total numbers of CD4+ and CD8+ T cells tended to be lower in the severe group at the third week of illness. Expressions of Ki-67, PD-1, perforin, and granzyme B in CD4+ or CD8+ T cells were significantly higher in the severe group than in the mild group at the third week. In contrast to the mild group, the levels of their expression did not decrease in the severe group.

CONCLUSIONS Severe COVID-19 had a higher degree of proliferation, activation, and cytotoxicity of T-cells at the late phase of illness without cytotoxic T-cell contraction, which might contribute to the development of severe COVID-19.

Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Keywords

COVID-19ContractionCytotoxic T cellGranzyme BPerforinSeverity

Figures

Figure 1
Figure 1 Leukocyte populations and CD4+ and CD8+ T cell counts and Ki-67 expressions at the third week of illness in 12 patients with COVID-19 according to severity. (A) The counts (cells/μL) of neutrophils, lymphocyte, and monocytes in severe (n = 4, open circle) or mild cases (n = 8, closed circle). (B) Frequencies and counts (cells/μL) of CD4+ and CD8+ T cells. (C) Ki-67 expressions in CD4+ and CD8+ T cells. (D) Representative dot plots show the identification of Ki-67+, HLA-DR+, PD-1+, or CD38+ cells in CD4+ (1st line of each panel) or CD8+ (2nd line of each panel) T cells in severe (upper panels) or mild (lower panels) cases. Bars denote mean values. Gray boxes represent interquartile ranges of healthy controls.
Figure 2
Figure 2 Expressions of activation markers and FoxP3+ CD4+ T cells at the third week of illness according to severity. (A) HLA-DR, PD-1, and CD38 expressions in CD4+ and CD8+ T cells, in severe (n = 4, open circle) and mild cases (n = 8, closed circle). (B) Frequencies of FoxP3+CD4+ T cells and representative dot plots showing the identification of the population. Bars denote mean values. Gray boxes represent interquartile ranges of healthy controls.
Figure 3
Figure 3 Effector granules or cytokine expressions at the third week of illness according to severity. (A) Perforin or granzyme B expressions in severe (n = 4, open circle) and mild cases (n = 8, closed circle) and representative dot plots showing the identification of perforin+, granzyme B+, IL-7Rαhigh, or IL-7Rαlow cells in CD4+ or CD8+ T cells in severe (upper panels) or mild (lower panels) cases. (B) Frequencies of IL-7Rαlow effector memory (CCR7-CD45RA+/−) CD8+ T cells and representative histograms. (C) IFN-γ, IL-2, IL-4, and IL-17 expressions in CD4+ and CD8+ T cells and representative dot plots showing the identification of IFN-γ+, IL-2+, IL-4+, and IL-17+ cells in CD4+ or CD8+ T cells in severe (upper panels) or mild (lower panels) cases. Bars denote mean values. Gray boxes represent interquartile ranges of healthy controls.
Figure 4
Figure 4 Temporal changes of cell-mediated immune responses in 11 patients with COVID-19 according to severity. Frequencies of Ki-67+, PD-1+, perforin+, granzyme B+ CD8+ T cells, and IL-7Rαlow effector memory CD8+ T cells in severe (n = 3) or mild (n = 8) cases from the first week (closed circle) to the third week (open circle).

그림 출처: PubMed Central 공개 논문 (PMC7261468)

그 밖의 정보
출판 형태
Journal Article
저널
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · eISSN 1878-3511
전자 출판
2020-05-31
MeSH
Adult · Aged · Aged, 80 and over · Betacoronavirus · CD4-Positive T-Lymphocytes / immunology · CD8-Positive T-Lymphocytes / immunology · COVID-19 · Coronavirus Infections / immunology / physiopathology · Cytokines / immunology · Female · Granzymes · Humans · Immunity, Cellular* · Ki-67 Antigen · Leukocytes, Mononuclear / immunology · Lymphocyte Activation* · Lymphocyte Count · Male · Middle Aged · Pandemics · Perforin · Pneumonia, Viral / immunology / physiopathology · Programmed Cell Death 1 Receptor · SARS-CoV-2 · T-Lymphocytes, Cytotoxic / immunology
Substances
Cytokines · Ki-67 Antigen · MKI67 protein, human · PDCD1 protein, human · Programmed Cell Death 1 Receptor · Perforin · GZMB protein, human · Granzymes
참고문헌
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