SUMMARY Although autoimmune disorders are a significant source of morbidity and mortality in older individuals, the mechanisms governing age-associated increases in susceptibility remain incompletely understood. Central T cell tolerance is mediated through presentation of self-antigens by cells constituting the thymic microenvironment, including epithelial cells, dendritic cells, and B cells. Medullary thymic epithelial cells (mTECs) and B cells express distinct cohorts of self-antigens, including tissue-restricted self-antigens (TRAs), such that developing T cells are tolerized to antigens from peripheral tissues. We find that expression of the TRA transcriptional regulator Aire, as well as Aire-dependent genes, declines with age in thymic B cells in mice and humans and that cell-intrinsic and cell-extrinsic mechanisms contribute to the diminished capacity of peripheral B cells to express Aire within the thymus. Our findings indicate that aging may diminish the ability of thymic B cells to tolerize T cells, revealing a potential mechanistic link between aging and autoimmunity.

BACKGROUND Using platelet additive solution (PAS) to dilute fibrinogen during long‐term cold storage of platelets (PLTs) decreases PLT activation and increases functional PLT shelf life. We performed a randomized, paired study to assess the in vitro quality of PLTs stored in the cold in T‐PAS+ for up to 18 days evaluated against PLTs stored under currently allowable conditions (5‐day room temperature–stored PLTs [RTP] and 3‐day cold‐stored PLTs [CSP]). STUDY DESIGN AND METHODS PLTs were collected from healthy volunteers (n = 10) and diluted to 65% T‐PAS+/35% plasma before cold storage. Double‐dose apheresis PLTs (in 100% plasma) were collected from the same donors and split into two bags (one bag RTP, one bag CSP). All bags were sampled on the day of collection (Day 0). CSP and RTP bags were sampled on Days 3 and 5, respectively. T‐PAS+ samples were assessed on Days 3, 5, 14, 16, and 18 of storage for metabolism, hemostatic function, and activation. RESULTS After 18 days of storage in T‐PAS+, pH was 6.71 ± 0.04, PLT count was comparable to Day 3 CSP, PLT function (aggregation and clot strength) was comparable to Day 5 RTP, and PLT activation was significantly increased. CONCLUSION Refrigerated PLTs stored in T‐PAS+ for 18 days met FDA pH standards. Functional metrics suggest activity of T‐PAS+‐stored PLTs and the potential to contribute to hemostasis throughout 18 days of storage. Extending the shelf life of PLTs would increase access to hemostatic resuscitation for bleeding patients in military and civilian settings.

Background: Platelets pose the greatest transfusion-transmitted infectious risk among blood products. Refrigeration of platelets can mitigate bacterial contamination and extend platelet shelf life. Implementation of pathogen reduction technologies (PRTs) at blood banks has become increasingly popular to protect against emerging and reemerging infectious diseases. In this study, we sought to evaluate the effects of Intercept PRT on platelets collected on different platforms and cold-stored for up to 21 days in plasma and platelet additive solution (PAS). Methods: Double-dose apheresis platelets were collected with use of a Trima or Amicus system into either 100% plasma or 65% InterSol PAS/35% plasma and split equally between two bags. One bag served as control, while the other received Intercept PRT treatment. Bags were stored unagitated in the cold and evaluated on Days 1, 7, 14, and 21 to assess platelet metabolism, activation, aggregation, and clot formation and retraction. Results: By Day 14 of storage, lactate levels reached approximately 13 mmol/L for all samples irrespective of Intercept treatment. Mean clot firmness dropped from the 62.2-to 67.5-mm range (Day 1) to the 28.4-to 51.3-mm range (Day 21), with no differences observed between groups. Clot weights of Intercepttreated Trima/plasma samples were significantly higher than control by Day 14 of storage (P = .004), indicating a reduced clot retraction function. Intercept treatment caused a higher incidence of plasma membrane breakdown in plasma-stored platelets (P = .0013; Trima/plasma Day 14 Control vs Intercept). Conclusions: Intercept treatment of platelets and subsequent cold storage, in plasma or PAS, results in comparable platelet metabolism platelets for up to 14 days of storage but altered clotting dynamics. Pathogen-reduced platelets with an extended shelf life would be beneficial for the deployed setting and would greatly impact transfusion practice among civilian transfusion centers.