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TOX is expressed by exhausted and polyfunctional human effector memory CD8(+) T cells
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- Sekine, Takuya (författare)
- Karolinska Institutet
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- Perez-Potti, Andre (författare)
- Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
- Nguyen, Son (författare)
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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
- Engelska.
- Ingår i: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 5:49
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- 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)
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