What is "exhaustion"? Take Tpex into account, and ghe Nobel prize 2018.
November 15, 2025 at 11:43 PM
What is "exhaustion"? Take Tpex into account, and ghe Nobel prize 2018.
Two studies published in @nature.com today showing that Tpex-like cells develop independent from acute or chronic infection
#Tpex
www.nature.com/articles/s41...
#Tpex
www.nature.com/articles/s41...
January 9, 2025 at 8:33 AM
Two studies published in @nature.com today showing that Tpex-like cells develop independent from acute or chronic infection
#Tpex
www.nature.com/articles/s41...
#Tpex
www.nature.com/articles/s41...
Am I the only one that finds the evolution of the 'Tpex' concept a bit confusing? two new papers on this in Nature: www.nature.com/articles/s41...
www.nature.com/articles/s41...
www.nature.com/articles/s41...
An early precursor CD8 T cell that adapts to acute or chronic viral infection - Nature
Nature - An early precursor CD8 T cell that adapts to acute or chronic viral infection
www.nature.com
January 9, 2025 at 11:00 AM
Am I the only one that finds the evolution of the 'Tpex' concept a bit confusing? two new papers on this in Nature: www.nature.com/articles/s41...
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Excited for our lab's FIRST paper #ScienceImmunology! 🎉
Led by @categraca.bsky.social & Amania Sheikh, with amazing collabs from Axel Kallies, Dane Newman, & @rickyjohnstone.bsky.social
Huge thanks to reviewers & @claireolingy.bsky.social 🙌
#Tpex #onthescoreboard
www.science.org/doi/full/10....
Led by @categraca.bsky.social & Amania Sheikh, with amazing collabs from Axel Kallies, Dane Newman, & @rickyjohnstone.bsky.social
Huge thanks to reviewers & @claireolingy.bsky.social 🙌
#Tpex #onthescoreboard
www.science.org/doi/full/10....
Stem-like memory and precursors of exhausted T cells share a common progenitor defined by ID3 expression
ID3 defines stem-like T cells with high developmental potential that sustain T cell responses to chronic infection and cancer.
www.science.org
January 31, 2025 at 7:51 PM
Excited for our lab's FIRST paper #ScienceImmunology! 🎉
Led by @categraca.bsky.social & Amania Sheikh, with amazing collabs from Axel Kallies, Dane Newman, & @rickyjohnstone.bsky.social
Huge thanks to reviewers & @claireolingy.bsky.social 🙌
#Tpex #onthescoreboard
www.science.org/doi/full/10....
Led by @categraca.bsky.social & Amania Sheikh, with amazing collabs from Axel Kallies, Dane Newman, & @rickyjohnstone.bsky.social
Huge thanks to reviewers & @claireolingy.bsky.social 🙌
#Tpex #onthescoreboard
www.science.org/doi/full/10....
Overlaying scRNAseq with Totalseq, we could not only define the transcriptional Tpex and Tscm cell signatures, but cell surface markers that tracked conversion between these transient populations.
March 11, 2025 at 3:26 AM
Overlaying scRNAseq with Totalseq, we could not only define the transcriptional Tpex and Tscm cell signatures, but cell surface markers that tracked conversion between these transient populations.
Got to love a good #Tpex viewpoint!
New insights into progenitor exhausted T cell populations
New insights into progenitor exhausted T cell populations
Nature Reviews Immunology, Published online: 30 June 2026; doi:10.1038/s41577-026-01328-9In this Viewpoint, eight experts from the field of T cell exhaustion discuss current understanding of the self-renewing population of PD1+TCF1+TOX+ precursor and/or progenitor exhausted CD8+ T cells and controversies related to their development and function.
dlvr.it
June 30, 2026 at 1:19 PM
Got to love a good #Tpex viewpoint!
Exhaustion unfolds hierarchically: TPEX → TEXint → TEXterm.
Critically, TPEX cells are self‑renewing, multipotent, and therapy‑responsive; they sustain the response rather than representing dysfunction or fatigue.
2/6
Critically, TPEX cells are self‑renewing, multipotent, and therapy‑responsive; they sustain the response rather than representing dysfunction or fatigue.
2/6
June 17, 2026 at 1:47 PM
Exhaustion unfolds hierarchically: TPEX → TEXint → TEXterm.
Critically, TPEX cells are self‑renewing, multipotent, and therapy‑responsive; they sustain the response rather than representing dysfunction or fatigue.
2/6
Critically, TPEX cells are self‑renewing, multipotent, and therapy‑responsive; they sustain the response rather than representing dysfunction or fatigue.
2/6
The Type VI secretion effector TpeX expands the pore-forming virulence arsenal of Pseudomonas aeruginosa https://www.biorxiv.org/content/10.64898/2026.08.24.746647v1
August 25, 2026 at 4:17 AM
The Type VI secretion effector TpeX expands the pore-forming virulence arsenal of Pseudomonas aeruginosa https://www.biorxiv.org/content/10.64898/2026.08.24.746647v1
Cool new study from the lab of my friend and collaborator @danielutzschneider.bsky.social in #ScienceImmunology showing that a common ID3+ precursor gives rise to stem-like memory and Tpex cells. Congrats to everyone involved!! @rickyjohnstone.bsky.social @petermaccc.bsky.social @onjcri.org.au
Excited for our lab's FIRST paper #ScienceImmunology! 🎉
Led by @categraca.bsky.social & Amania Sheikh, with amazing collabs from Axel Kallies, Dane Newman, & @rickyjohnstone.bsky.social
Huge thanks to reviewers & @claireolingy.bsky.social 🙌
#Tpex #onthescoreboard
www.science.org/doi/full/10....
Led by @categraca.bsky.social & Amania Sheikh, with amazing collabs from Axel Kallies, Dane Newman, & @rickyjohnstone.bsky.social
Huge thanks to reviewers & @claireolingy.bsky.social 🙌
#Tpex #onthescoreboard
www.science.org/doi/full/10....
Stem-like memory and precursors of exhausted T cells share a common progenitor defined by ID3 expression
ID3 defines stem-like T cells with high developmental potential that sustain T cell responses to chronic infection and cancer.
www.science.org
January 31, 2025 at 10:16 PM
Cool new study from the lab of my friend and collaborator @danielutzschneider.bsky.social in #ScienceImmunology showing that a common ID3+ precursor gives rise to stem-like memory and Tpex cells. Congrats to everyone involved!! @rickyjohnstone.bsky.social @petermaccc.bsky.social @onjcri.org.au
Our paper is out! Check out this beautiful story where we uncovered that the costimulatory molecule ICOS is detrimental for PD-1+ CD8 T cells.
Sustained ICOS signaling reduces memory-like features of progenitor exhausted CD8 T cells in chronic viral infection and liver cancer.
Sustained ICOS signaling reduces memory-like features of progenitor exhausted CD8 T cells in chronic viral infection and liver cancer.
July 8, 2025 at 1:05 PM
Our paper is out! Check out this beautiful story where we uncovered that the costimulatory molecule ICOS is detrimental for PD-1+ CD8 T cells.
Sustained ICOS signaling reduces memory-like features of progenitor exhausted CD8 T cells in chronic viral infection and liver cancer.
Sustained ICOS signaling reduces memory-like features of progenitor exhausted CD8 T cells in chronic viral infection and liver cancer.
Further, we tracked the plasticity of these two cell states, with antigen availability dictating the transition between CD61+ Tpex and CD55+ Tscm cell states.
March 11, 2025 at 3:26 AM
Further, we tracked the plasticity of these two cell states, with antigen availability dictating the transition between CD61+ Tpex and CD55+ Tscm cell states.
Online now: The costimulatory molecule ICOS limits memory-like properties and function of exhausted PD-1+CD8+ T cells
The costimulatory molecule ICOS limits memory-like properties and function of exhausted PD-1+CD8+ T cells
Understanding regulation of progenitor exhausted CD8+ T (Tpex) cell differentiation is important for immunotherapies. Humblin et al. report that sustained ICOS costimulation is detrimental to PD-1+CD8+ T cell responses. Limiting ICOS signaling enhances Tpex cell stemness and differentiation into effector-like cells with improved survival and functionality. ICOSL blockade reinvigorates PD-1+CD8+ T cells and promotes viral or tumor control, potentiating PD-1 targeted immunotherapy.
dlvr.it
July 7, 2025 at 2:49 PM
Online now: The costimulatory molecule ICOS limits memory-like properties and function of exhausted PD-1+CD8+ T cells
youtube.com/watch?v=tpEX...
George Hit On Me when He Played Nicholls State University in Thibodeaux, La…I was Dating my Future Husband at the time, but Was Flattered! Knowing what I Know Now…I Should Have Gone w/ George…! Regrets Are Few, but That Was One!
George Hit On Me when He Played Nicholls State University in Thibodeaux, La…I was Dating my Future Husband at the time, but Was Flattered! Knowing what I Know Now…I Should Have Gone w/ George…! Regrets Are Few, but That Was One!
George Carlin Tried To Warn You.. He Wasn't Joking
YouTube video by Patrick Cc:
youtube.com
August 14, 2025 at 1:23 AM
youtube.com/watch?v=tpEX...
George Hit On Me when He Played Nicholls State University in Thibodeaux, La…I was Dating my Future Husband at the time, but Was Flattered! Knowing what I Know Now…I Should Have Gone w/ George…! Regrets Are Few, but That Was One!
George Hit On Me when He Played Nicholls State University in Thibodeaux, La…I was Dating my Future Husband at the time, but Was Flattered! Knowing what I Know Now…I Should Have Gone w/ George…! Regrets Are Few, but That Was One!
Using single-cell RNA sequencing, Gago da Graça, Sheikh, and Newman et al. investigated developmental relationships between stem-like memory T cells and Tpex cells, and their roles in infection and cancer. bit.ly/41aDA52 @thedohertyinst.bsky.social
February 17, 2025 at 12:45 PM
Using single-cell RNA sequencing, Gago da Graça, Sheikh, and Newman et al. investigated developmental relationships between stem-like memory T cells and Tpex cells, and their roles in infection and cancer. bit.ly/41aDA52 @thedohertyinst.bsky.social
We looked at this differentiation in detail to show that at day 8 post infection, IFN-I blocked stem-like cells appear similar to Tpex cells seen in chronic infection. After viral clearance, the population resemble Tscm, the transition associated with decreased inhibitory receptor expression.
March 11, 2025 at 3:26 AM
We looked at this differentiation in detail to show that at day 8 post infection, IFN-I blocked stem-like cells appear similar to Tpex cells seen in chronic infection. After viral clearance, the population resemble Tscm, the transition associated with decreased inhibitory receptor expression.
…(ii) Adoptively transferred Tmem33-/- (KO) OT-I CD8+ T cells massively expand in B16F10-OVA and show greater Tpex accumulation in tumours and draining lymph nodes compared to Tmem33+/+ (WT) OT-I (thank you @witherslab.bsky.social )…. 6/10
January 5, 2026 at 3:30 PM
…(ii) Adoptively transferred Tmem33-/- (KO) OT-I CD8+ T cells massively expand in B16F10-OVA and show greater Tpex accumulation in tumours and draining lymph nodes compared to Tmem33+/+ (WT) OT-I (thank you @witherslab.bsky.social )…. 6/10
Ngl running just Toxapex Corviknight and Swampert(rindo), you dont really need megas. Just tank everything. Swampert(rindo) checks so much shit, then Tpex and corv can sit in front of a lot of threats and just wear them out slowly. Why bother with high power beasts when you can just comfortably sit?
July 19, 2026 at 4:18 AM
Ngl running just Toxapex Corviknight and Swampert(rindo), you dont really need megas. Just tank everything. Swampert(rindo) checks so much shit, then Tpex and corv can sit in front of a lot of threats and just wear them out slowly. Why bother with high power beasts when you can just comfortably sit?
Mettl8 maintains stem-like TPEX cells by stabilizing Tcf1 via m3C modification and facilitating chromatin looping at the Tox locus @jem.org
rupress.org/jem/article/...
rupress.org/jem/article/...
March 29, 2026 at 3:30 PM
Mettl8 maintains stem-like TPEX cells by stabilizing Tcf1 via m3C modification and facilitating chromatin looping at the Tox locus @jem.org
rupress.org/jem/article/...
rupress.org/jem/article/...
PD-1 blockade drug holiday improves exhausted progenitor CD8 T cell (Tpex) reinvigoration by avoiding Tpex adaptive resistance https://www.biorxiv.org/content/10.64898/2026.05.14.725199v1
May 18, 2026 at 6:16 PM
PD-1 blockade drug holiday improves exhausted progenitor CD8 T cell (Tpex) reinvigoration by avoiding Tpex adaptive resistance https://www.biorxiv.org/content/10.64898/2026.05.14.725199v1
TCF-1+ stem-like CD8+ T cells encompass two populations with therapeutic potential:
1. Tscm cells – seen in vaccine and acute infection
2. Tpex cells – seen in chronic infection and cancer
But their developmental relationship and how to individually define or promote them is lacking.
1. Tscm cells – seen in vaccine and acute infection
2. Tpex cells – seen in chronic infection and cancer
But their developmental relationship and how to individually define or promote them is lacking.
March 11, 2025 at 3:26 AM
TCF-1+ stem-like CD8+ T cells encompass two populations with therapeutic potential:
1. Tscm cells – seen in vaccine and acute infection
2. Tpex cells – seen in chronic infection and cancer
But their developmental relationship and how to individually define or promote them is lacking.
1. Tscm cells – seen in vaccine and acute infection
2. Tpex cells – seen in chronic infection and cancer
But their developmental relationship and how to individually define or promote them is lacking.
Checkpoint blockade doesn’t “reinvigorate exhaustion.” It mainly works by expanding and redirecting the TPEX pool, may affect other subsets, and not by reprogramming terminally exhausted cells with a more fixed epigenetic state.
5/6
5/6
June 17, 2026 at 1:48 PM
Checkpoint blockade doesn’t “reinvigorate exhaustion.” It mainly works by expanding and redirecting the TPEX pool, may affect other subsets, and not by reprogramming terminally exhausted cells with a more fixed epigenetic state.
5/6
5/6
Combined:
⭐️ CD8+ T cells primed in the absence of IFN-I signaling transition from Tpex to Tscm cells.
⭐️ These are plastic cellular states, with antigen availability dictating the transition between the two.
⭐️ We propose this natural transition promotes development of potent CD8+ memory formation.
⭐️ CD8+ T cells primed in the absence of IFN-I signaling transition from Tpex to Tscm cells.
⭐️ These are plastic cellular states, with antigen availability dictating the transition between the two.
⭐️ We propose this natural transition promotes development of potent CD8+ memory formation.
March 11, 2025 at 3:26 AM
Combined:
⭐️ CD8+ T cells primed in the absence of IFN-I signaling transition from Tpex to Tscm cells.
⭐️ These are plastic cellular states, with antigen availability dictating the transition between the two.
⭐️ We propose this natural transition promotes development of potent CD8+ memory formation.
⭐️ CD8+ T cells primed in the absence of IFN-I signaling transition from Tpex to Tscm cells.
⭐️ These are plastic cellular states, with antigen availability dictating the transition between the two.
⭐️ We propose this natural transition promotes development of potent CD8+ memory formation.