Publisher Correction: Metabolic characteristics of CD8+ T cell subsets in young and aged individuals are not predictive of functionality

Quinn, Kylie M.; Hussain, Tabinda; Kraus, Felix; Formosa, Luke E.; Lam, Wai Kit; Dagley, Michael J; Saunders, Eleanor; Assmus, Lisa Mareike; Wynne-Jones, Erica; Loh, Liyen; Sandt, Carolien E. van de; Cooper, Lucy; Good-Jacobson, Kim L; Kedzierska, Katherine; Mackay, Laura K.; McConville, Malcolm J.; Ramm, Georg; Ryan, Michael; Gruta, Nicole L. La

doi:10.1038/s41467-020-17441-9

Cited by 2 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also observed a trend for increased mitochondrial SRC in CDK6-deficient CD8+ T cells. The significance of SRC and mitochondrial biogenesis for CD8+ T cell effector function is discussed controversially ( 48 , 69 ). We failed to observe a link between mitochondrial metabolic activity and CD8+ T cell-mediated cytotoxicity and production of the effector cytokines IFN-γ and TNF-α in vitro .…”

Section: Discussionmentioning

confidence: 99%

T Cell-Intrinsic CDK6 Is Dispensable for Anti-Viral and Anti-Tumor Responses In Vivo

et al. 2021

View full text Add to dashboard Cite

The cyclin-dependent kinase 6 (CDK6) regulates the transition through the G1-phase of the cell cycle, but also acts as a transcriptional regulator. As such CDK6 regulates cell survival or cytokine secretion together with STATs, AP-1 or NF-κB. In the hematopoietic system, CDK6 regulates T cell development and promotes leukemia and lymphoma. CDK4/6 kinase inhibitors are FDA approved for treatment of breast cancer patients and have been reported to enhance T cell-mediated anti-tumor immunity. The involvement of CDK6 in T cell functions remains enigmatic. We here investigated the role of CDK6 in CD8+ T cells, using previously generated CDK6 knockout (Cdk6-/-) and kinase-dead mutant CDK6 (Cdk6K43M) knock-in mice. RNA-seq analysis indicated a role of CDK6 in T cell metabolism and interferon (IFN) signaling. To investigate whether these CDK6 functions are T cell-intrinsic, we generated a T cell-specific CDK6 knockout mouse model (Cdk6fl/fl CD4-Cre). T cell-intrinsic loss of CDK6 enhanced mitochondrial respiration in CD8+ T cells, but did not impact on cytotoxicity and production of the effector cytokines IFN-γ and TNF-α by CD8+ T cells in vitro. Loss of CDK6 in peripheral T cells did not affect tumor surveillance of MC38 tumors in vivo. Similarly, while we observed an impaired induction of early responses to type I IFN in CDK6-deficient CD8+ T cells, we failed to observe any differences in the response to LCMV infection upon T cell-intrinsic loss of CDK6 in vivo. This apparent contradiction might at least partially be explained by the reduced expression of Socs1, a negative regulator of IFN signaling, in CDK6-deficient CD8+ T cells. Therefore, our data are in line with a dual role of CDK6 in IFN signaling; while CDK6 promotes early IFN responses, it is also involved in the induction of a negative feedback loop. These data assign CDK6 a role in the fine-tuning of cytokine responses.

show abstract

Section: Discussionmentioning

confidence: 99%

T Cell-Intrinsic CDK6 Is Dispensable for Anti-Viral and Anti-Tumor Responses In Vivo

et al. 2021

View full text Add to dashboard Cite

show abstract

Senescent T Cells in Age-Related Diseases

Yu,

Zhou,

Liu

et al. 2024

Aging and disease

View full text Add to dashboard Cite

Age-induced alterations in human immunity are often considered deleterious and are referred to as immunosenescence. The immune system monitors the number of senescent cells in the body, while immunosenescence may represent the initiation of systemic aging. Immune cells, particularly T cells, are the most impacted and involved in age-related immune function deterioration, making older individuals more prone to different age-related diseases. T-cell senescence can impact the effectiveness of immunotherapies that rely on the immune system's function, including vaccines and adoptive T-cell therapies. The research and practice of using senescent T cells as therapeutic targets to intervene in age-related diseases are in their nascent stages. Therefore, in this review, we summarize recent related literature to investigate the characteristics of senescent T cells as well as their formation mechanisms, relationship with various aging-related diseases, and means of intervention. The primary objective of this article is to explore the prospects and possibilities of therapeutically targeting senescent T cells, serving as a valuable resource for the development of immunotherapy and treatment of age-related diseases.

show abstract

Publisher Correction: Metabolic characteristics of CD8+ T cell subsets in young and aged individuals are not predictive of functionality

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Cited by 2 publications

References 0 publications

T Cell-Intrinsic CDK6 Is Dispensable for Anti-Viral and Anti-Tumor Responses In Vivo

T Cell-Intrinsic CDK6 Is Dispensable for Anti-Viral and Anti-Tumor Responses In Vivo

Senescent T Cells in Age-Related Diseases

Contact Info

Product

Resources

About