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TOX is expressed by...
TOX is expressed by exhausted and polyfunctional human effector memory CD8(+) T cells
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- Sekine, Takuya (author)
- Karolinska Institutet
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- Perez-Potti, Andre (author)
- Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
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Nguyen, Son (author)
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- Gorin, Jean-Baptiste (author)
- Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
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- Wu, Vincent H. (author)
- Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA.
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- Gostick, Emma (author)
- Cardiff Univ, Univ Hosp Wales, Sch Med, Div Infect & Immun, Cardiff, Wales.
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- Llewellyn-Lacey, Sian (author)
- Cardiff Univ, Univ Hosp Wales, Sch Med, Div Infect & Immun, Cardiff, Wales.
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- Hammer, Quirin (author)
- Karolinska Institutet
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- Falck-Jones, Sara (author)
- Karolinska Institutet
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- Vangeti, Sindhu (author)
- Karolinska Inst, Dept Med Solna, Div Immunol & Allergy, Stockholm, Sweden.
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- Yu, Meng (author)
- Karolinska Inst, Dept Med Solna, Div Immunol & Allergy, Stockholm, Sweden.
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- Smed-Sorensen, Anna (author)
- Karolinska Institutet
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- Gaballa, Ahmed (author)
- Karolinska Institutet
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- Uhlin, Michael (author)
- Karolinska Institutet,KTH,Biofysik,Science for Life Laboratory, SciLifeLab,Karolinska Univ Hosp, Dept Immunol & Transfus Med, Stockholm, Sweden.
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- Sandberg, Johan K. (author)
- Karolinska Institutet
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- Brander, Christian (author)
- IrsiCaixa AIDS Res Inst, Badalona, Spain.;Univ Cent Catalunya, Univ Vic, Vic, Spain.;ICREA, Barcelona, Spain.
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- Nowak, Piotr (author)
- Karolinska Institutet
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- Goepfert, Paul A. (author)
- Univ Alabama Birmingham, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA.
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- Price, David A. (author)
- Cardiff Univ, Univ Hosp Wales, Sch Med, Div Infect & Immun, Cardiff, Wales.;Cardiff Univ, Univ Hosp Wales, Sch Med, Syst Immun Res Inst, Cardiff, Wales.
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- Betts, Michael R. (author)
- Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA.
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- Buggert, Marcus (author)
- Karolinska Institutet
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Karolinska Institutet Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden (creator_code:org_t)
- American Association for the Advancement of Science (AAAS), 2020
- 2020
- English.
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In: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 5:49
- Related links:
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https://doi.org/10.1...
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https://orca.cardiff...
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https://urn.kb.se/re...
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Abstract
Subject headings
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- CD8(+) T cell exhaustion is a hallmark of many cancers and chronic infections. In mice, T cell factor 1 (TCF-1) maintains exhausted CD8(+) T cell responses, whereas thymocyte selection-associated HMG box (TOX) is required for the epigenetic remodeling and survival of exhausted CD8(+) T cells. However, it has remained unclear to what extent these transcription factors play analogous roles in humans. In this study, we mapped the expression of TOX and TCF-1 as a function of differentiation and specificity in the human CD8(+) T cell landscape. Here, we demonstrate that circulating TOX+ CD8(+) T cells exist in most humans, but that TOX is not exclusively associated with exhaustion. Effector memory CD8(+) T cells generally expressed TOX, whereas naive and early-differentiated memory CD8(+) T cells generally expressed TCF-1. Cytolytic gene and protein expression signatures were also defined by the expression of TOX. In the context of a relentless immune challenge, exhausted HIV-specific CD8(+) T cells commonly expressed TOX, often in clusters with various activation markers and inhibitory receptors, and expressed less TCF-1. However, polyfunctional memory CD8(+) T cells specific for cytomegalovirus (CMV) or Epstein-Barr virus (EBV) also expressed TOX, either with or without TCF-1. A similar phenotype was observed among HIV-specific CD8(+) T cells from individuals who maintained exceptional immune control of viral replication. Collectively, these data demonstrate that TOX is expressed by most circulating effector memory CD8(+) T cell subsets and not exclusively linked to exhaustion.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Sekine, Takuya
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Perez-Potti, And ...
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Nguyen, Son
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Gorin, Jean-Bapt ...
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Wu, Vincent H.
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Gostick, Emma
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show more...
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Llewellyn-Lacey, ...
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Hammer, Quirin
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Falck-Jones, Sar ...
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Vangeti, Sindhu
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Yu, Meng
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Smed-Sorensen, A ...
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Gaballa, Ahmed
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Uhlin, Michael
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Sandberg, Johan ...
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Brander, Christi ...
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Nowak, Piotr
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Goepfert, Paul A ...
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Price, David A.
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Betts, Michael R ...
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Buggert, Marcus
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
- Articles in the publication
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Science immunolo ...
- By the university
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Royal Institute of Technology
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Karolinska Institutet