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 EGFR ^hi 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 use 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.

Senecavirus A (SVA) is an endemic pathogen with ongoing relevance to the U.S. swine industry due to its clinical resemblance to foot-and-mouth disease (FMD) and its potential impact on animal health and trade. This study analyzes the incidence and geographic distribution of SVA outbreaks in U.S. breeding herds from January 2015 to December 2024. We used enhanced surveillance by combining diagnostic data from veterinary diagnostic laboratories and practitioners’ reports to assess SVA incidence, identifying temporal fluctuations and regional patterns. Our findings indicate that the cumulative incidence of SVA in U.S. breeding herds is low overall (<2.5% per year), with peak incidence observed during the third and fourth quarters of the calendar year. Outbreaks are more frequently reported in the Midwest. Our results suggest potential seasonality or regional factors influencing disease transmission. The median time interval between SVA outbreaks for sites experiencing more than one outbreak is 402 days. This study provides valuable insights into the current epidemiology of SVA in U.S. breeding herds, and highlights the need for continued monitoring and preparedness to prevent future outbreaks.