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Background Liver parenchymal cell allografts initiate both CD4-dependent and CD4-independent, CD8+ T cell-mediated acute rejection pathways. The magnitude of allospecific CD8+ T cell in vivo cytotoxic effector function is maximal when primed in the presence of CD4+ T cells. The current studies were conducted to determine if and how CD4+ T cells might influence cytotoxic effector mechanisms. Methods Mice were transplanted with allogeneic hepatocytes. In vivo cytotoxicity assays and various gene-deficient recipient mice and target cells were utilized to determine the development of Fas-, TNF-α-, and perforin-dependent cytotoxic effectors mechanisms following transplantation. Results CD8+ T cells maturing in CD4-sufficient hepatocyte recipients develop multiple (Fas-, TNF-α-, and perforin-mediated) cytotoxic mechanisms. However, CD8+ T cells, maturing in the absence of CD4+ T cells, mediate cytotoxicity and transplant rejection that is exclusively TNF-α/TNFR-dependent. To determine the kinetics of CD4-mediated help, CD4+ T cells were adoptively transferred into CD4-deficient mice at various times posttransplant. The maximal influence of CD4+ T cells on the magnitude of CD8-mediated in vivo allocytotoxicity occurs within 48 hours. Conclusion The implication of these studies is that interference of CD4+ T cell function by disease or immunotherapy will have downstream consequences on both the magnitude of allocytotoxicity as well as the cytotoxic effector mechanisms employed by allospecific CD8+ cytolytic T cells.

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Background The perioperative anesthesia care during subcutaneous implantable cardioverter‐defibrillator (S‐ICD) implantation is still evolving. Objective To assess the feasibility and safety of S‐ICD implantation with monitored anesthesia care (MAC) versus general anesthesia (GA) in a tertiary care center. Methods This is a single‐center retrospective study of patients undergoing S‐ICD implantation between October 2012 and May 2019. Patients were categorized into MAC and GA group based on the mode of anesthesia. Procedural success without escalation to GA was the primary endpoint of the study, whereas intraprocedural hemodynamics, need of pharmacological support for hypotension and bradycardia, length of the procedure, stay in the post‐anesthesia care unit, and postoperative pain were assessed as secondary endpoints. Results The study comprises 287 patients with MAC in 111 and GA in 176 patients. Compared to MAC, patients in GA group were younger and had a higher body mass index. All patients had successful S‐ICD implantation. Only one patient (0.9%) in the MAC group was converted to GA. Despite a similar baseline heart rate (HR) and mean arterial blood pressure (MAP) in both groups, patients with GA had significantly lower HR and MAP during the procedure and more frequently required pharmacological hemodynamic support. Length of the procedure, stay in the postanesthesia care unit, and postoperative pain was similar in both groups. Conclusion This retrospective experience suggests that implantation of S‐ICD is feasible and safe with MAC. Use of GA is associated with more frequent administration of hemodynamic drugs during S‐ICD implantation.