immgenT CD4: A Reference Landscape of Mouse CD4+ T Cells
- 1University of Chicago
Abstract
CD4+ T cells are orchestrators of the immune system with diverse effector functions. Their full molecular diversity remains unclear due to the lack of a unified framework. Within the immgenT project, we profiled RNA, surface markers, and TCR clonotypes in conventional CD4+ T cells across >700 samples. Integration with a joint RNA-protein deep generative model revealed an ensemble of 20 CD4 states that account for all cells across tissues and challenges. Small, highly polarized clusters ("tips") that evoke Th1, Th2, Th17, and Tfh states co-exist with a majority of activated cells with mixed programs occupying "midland" states. Unlike CD8+ T cells, memory CD4+ cells largely mapped to the same states as effectors. Resting states proved quite diverse, and we uncovered unexpected similarities between Tfh and chronically stimulated states. Together, immgenT provides a unified molecular reference for CD4+ T cell diversity.
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BibTeX
@misc{mehrotra2026immgent,
title = {{immgenT CD4: A Reference Landscape of Mouse CD4+ T Cells}},
author = {N. Mehrotra and D. Bangs and A. L. Figueroa and G. C. Wei Bee and R. Lai and T. Shinkawa and K. C. Osum and A. Freuchet and Z. Zhang and L. Nogueira and T. Heim and K. J. Cadwell and M. Starnbach and S. Behar and S. Spranger and M. Pepper and M. K. Jenkins and J. Merkenschlager and C. Benoist and D. Zemmour and the immgenT project},
howpublished = {bioRxiv},
year = {2026},
month = may,
doi = {10.64898/2026.05.29.728553},
url = {https://www.biorxiv.org/content/10.64898/2026.05.29.728553v3},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - immgenT CD4: A Reference Landscape of Mouse CD4+ T Cells
AU - N. Mehrotra
AU - D. Bangs
AU - A. L. Figueroa
AU - G. C. Wei Bee
AU - R. Lai
AU - T. Shinkawa
AU - K. C. Osum
AU - A. Freuchet
AU - Z. Zhang
AU - L. Nogueira
AU - T. Heim
AU - K. J. Cadwell
AU - M. Starnbach
AU - S. Behar
AU - S. Spranger
AU - M. Pepper
AU - M. K. Jenkins
AU - J. Merkenschlager
AU - C. Benoist
AU - D. Zemmour
AU - the immgenT project
PY - 2026
DA - 2026/05/29
PB - bioRxiv
DO - 10.64898/2026.05.29.728553
UR - https://www.biorxiv.org/content/10.64898/2026.05.29.728553v3
AB - CD4+ T cells are orchestrators of the immune system with diverse effector functions. Their full molecular diversity remains unclear due to the lack of a unified framework. Within the immgenT project, we profiled RNA, surface markers, and TCR clonotypes in conventional CD4+ T cells across >700 samples. Integration with a joint RNA-protein deep generative model revealed an ensemble of 20 CD4 states that account for all cells across tissues and challenges. Small, highly polarized clusters ("tips") that evoke Th1, Th2, Th17, and Tfh states co-exist with a majority of activated cells with mixed programs occupying "midland" states. Unlike CD8+ T cells, memory CD4+ cells largely mapped to the same states as effectors. Resting states proved quite diverse, and we uncovered unexpected similarities between Tfh and chronically stimulated states. Together, immgenT provides a unified molecular reference for CD4+ T cell diversity.
ER -