The CD8 immgenT framework as a universal reference of mouse CD8αβ T cell differentiation states
Mouse CD8 T cell differentiation has been studied extensively in models of infections and cancer, yet no unified framework spans the full spectrum of immunological contexts. We present the CD8 immgenT framework, integrating >200,000 single-cell transcriptomes and 128-plex surface proteomes from 734 samples spanning multiple perturbations, tissues, and timepoints. Unbiased analysis identifies 21 states encompassing naive, effector, circulating memory, tissue-resident memory, progenitor-exhausted, and terminally-exhausted compartments, among others. These states re-emerge with striking molecular convergence across acute/chronic infections, cancer, autoimmunity, aging, and homeostasis, showing that near-identical transcriptional programs support protective or dysfunctional outcomes depending on developmental history and microenvironment. Classic archetypes map to discrete clusters but exhibit unappreciated heterogeneity and overlap, cautioning against rigid nomenclature. We provide validated combinatorial markers, flow cytometry gating strategies, and immgenT reference-based integration for reproducible annotation of new datasets. This universal coordinate system harmonizes fragmented CD8 T cell literature and clarifies relationships across diverse immune challenges.
Authors
- Nicole E. Scharping (ORCID: https://orcid.org/0000-0001-9373-4617)
- Kennidy K. Takehara (ORCID: https://orcid.org/0000-0002-1990-155X)
- Tomoyo Shinkawa
- Samuel M. Behar (ORCID: https://orcid.org/0000-0002-3374-6699)
- Shuozhi Liu (ORCID: https://orcid.org/0000-0002-9067-1195)
- Susan M. Kaech
- Ananda W. Goldrath (ORCID: https://orcid.org/0000-0002-5900-508X)
- Samantha Borys (ORCID: https://orcid.org/0000-0003-4960-131X)
- Amir Ferry (ORCID: https://orcid.org/0000-0003-2884-083X)
- Olga Barreiro
- Anna-Maria Globig (ORCID: https://orcid.org/0000-0002-5236-7459)
- Sara Quon (ORCID: https://orcid.org/0000-0003-3860-3491)
- Kitty P. Cheung
- Giovanni Galletti (ORCID: https://orcid.org/0000-0001-6613-2354)
- Ellen Duong (ORCID: https://orcid.org/0000-0002-4015-7112)
- David Zemmour
- Odhran Casey
- Taylor Heim
- Alexander Troy Monell
- Dhruv Patravali
Institutions
- Salk Institute for Biological Studies (US)
- Harvard University (US)
- University of Massachusetts Chan Medical School (US)
- Brown University (US)
- Ragon Institute of MGH, MIT and Harvard (US)
- University of California San Diego (US)
- University of Chicago (US)
- Allen Institute for Immunology (US)
- IIT@MIT (US)
- Allen Institute (US)
- Koch Institute for Integrative Cancer Research At MIT (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-02-04
- DOI
- https://doi.org/10.64898/2026.02.02.703365
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 0.00