Data from: Allospecific splenic Tr1 cells drive effector T cell exhaustion through upregulated Areg-EGFR signaling to promote transplant tolerance

Inducing stable tolerance to transplants remains a challenge in
immunology. Previously, we induced tolerance to allogeneic islets in
nonhuman primates by preemptive alloantigen delivery to antigen-presenting
cells in situ. Here, mass cytometry phenotyping with incorporated
donor-derived MHC-I peptide-loaded MHC-II tetramers revealed accumulation
of allospecific CD4+ T cell clusters in the spleen of tolerant recipients.
Areg+Tr1 regulatory and terminally exhausted EGFRhi T (Tex) cells
represented the predominant allospecific subsets. Trajectory analysis
showed that antigen-experienced effector memory T cells differentiated
into suppressive Areg+Tr1 and EGFR+TOX+Nur77+TCF-1- Tex subsets. Cell-cell
communication mapping showed that exhausted and effector memory T cells
engaged with allospecific Tr1 cells via the Areg-EGFR axis. Gene silencing
studies confirmed that Tr1 cells utilize Areg-EGFR signaling to drive the
metabolic suppression and epigenetic reprogramming of CD4⁺ T cells through
a Nur77-dependent pathway. These findings point to the splenic Areg⁺Tr1
cell-EGFR⁺Teff cell axis as a critical immunoregulatory pathway in
peripheral transplant tolerance. Here we provide the raw and processed
CyTOF (mass cytometry by time of flight) data and R analysis scripts used
to arrive at these conclusions for each cell type mentioned above. CyTOF
data is provided as FCS-format files representing counts for thousands of
cells and up to 36 mass-tagged protein markers.