CD4 T cell-derived IL-2 counteracts rapamycin-mediated suppression of CD8 T cell effector differentiation in acute GvHD

Rapamycin, an mTOR inhibitor, is used to control alloreactive T cell responses, but its effects on differentiation of donor T cell subsets in vivo are not fully understood. We previously identified two major subsets of alloreactive CD8⁺ T cells that arise during acute GvHD, including TCF1⁺ progenitor-like and Tim-3⁺ terminal effector populations.

In this study, we examined how rapamycin influences the activation, circulation, and differentiation states of donor CD8⁺ T cells in murine acute GvHD models, both with and without donor CD4⁺ T cell help. Single-cell RNA sequencing was performed on donor-derived T cells collected from multiple experimental conditions to define the transcriptional programs associated with rapamycin treatment, CD4⁺ T cell involvement, and effector commitment.