immgenT CD4: A Reference Landscape of Mouse CD4+ T Cells

Nitya Mehrotra; Derek J. Bangs; Andrea Lebron Figueroa; Gavyn Chern Wei Bee; Rocky Lai; Tomoyo Shinkawa; Kevin C. Osum; Antoine Freuchet; Z Zhang; Lilian Nogueira; Taylor A. Heim; Ken Cadwell; Michael N. Starnbach; Samuel Behar; Stefani Spranger; Marion Pepper; Marc K. Jenkins; Julia Merkenschlager; Christophe O. Benoist; David Zemmour; the immgenT project

doi:10.64898/2026.05.29.728553

ImmunologybioRxivSep 9, 2026

Preprint

immgenT CD4: A Reference Landscape of Mouse CD4+ T Cells

Nitya Mehrotra iD, Derek J. Bangs iD, Andrea Lebron Figueroa, Gavyn Chern Wei Bee iD, Rocky Lai iD, Tomoyo Shinkawa, Kevin C. Osum iD, Antoine Freuchet iD, Z Zhang iD, Lilian Nogueira iD, Taylor A. Heim iD, Ken Cadwell iD, Michael N. Starnbach iD, Samuel Behar iD, Stefani Spranger iD, Marion Pepper iD, Marc K. Jenkins iD, Julia Merkenschlager iD, Christophe O. Benoist iD, David Zemmour iD, the immgenT project

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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