In recent years, the myocardium has been rediscovered under the lenses of immunology, and lymphocytes have been implicated in the pathogenesis of cardiomyopathies with different etiologies. Aging is an important risk factor for heart diseases, and it also has impact on the immune system. Thus, we sought to determine whether immunological activity would influence myocardial structure and function in elderly mice. Morphological, functional, and molecular analyses revealed that the age-related myocardial impairment occurs in parallel with shifts in the composition of tissueresident leukocytes and with an accumulation of activated CD4 + Foxp3 − (forkhead box P3) IFN-γ + T cells in the heart-draining lymph nodes. A comprehensive characterization of different aged immune-deficient mouse strains revealed that T cells significantly contribute to age-related myocardial inflammation and functional decline. Upon adoptive cell transfer, the T cells isolated from the mediastinal lymph node (med-LN) of aged animals exhibited increased cardiotropism, compared with cells purified from young donors or from other irrelevant sites. Nevertheless, these cells caused rather mild effects on cardiac functionality, indicating that myocardial aging might stem from a combination of intrinsic and extrinsic (immunological) factors. Taken together, the data herein presented indicate that heart-directed immune responses may spontaneously arise in the elderly, even in the absence of a clear tissue damage or concomitant infection. These observations might shed new light on the emerging role of T cells in myocardial diseases, which primarily affect the elderly population.T he myocardial cellular composition has been revisited in recent years, and leukocyte subsets residing in the healthy heart have been described (1-10). Cardiac-resident macrophages exhibiting an M2-like gene expression profile were found to be distributed in close association with the coronary vascular bed (3), and niches for dendritic cells (CD11c + MHC-II high CD80/86 low ) were found near the cardiac valves of the intact heart (1). It was also demonstrated that cardiac-resident MHCII + cells process and present myosin heavy chain-alpha-derived peptides under steady-state conditions (11, 12) and prime T cells ex vivo (1). However, whether lymphocytes can seed the intact myocardium and whether T-cell priming with myocardial antigens can occur in the absence of an infection or autoimmune myocarditis remain elusive.More recently, accumulating evidence indicated that noninfectious myocardial diseases are modulated by T cells. During the last couple of years, our group demonstrated that ischemic, sterile myocardial injuries can elicit lymphocyte activation directed against cardiac antigens (13-16). Our previous data, showing for the first time that CD4 + T cells reactive to cardiac components can foster the healing process that takes place after myocardial infarction, were corroborated by several other reports (13,15,(17)(18)(19)(20). However, these autoreactive T cells can also b...

he ongoing COVID-19 pandemic has resulted in significant morbidity and mortality, particularly for patients with chronic medical conditions. Orthotopic heart transplant (OHT) recipients are at increased risk of SARS-CoV-2 infection because of chronic immunosuppression and frequent comorbid disease. 1,2 SARS-CoV-2 infection in heart transplant recipients is associated with a high case fatality rate ranging from 10% to 35% and hospitalization rate ranging from 50% to 60%. 2,3 The US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for a a messenger RNA (mRNA) vaccine against COVID-19 on December 11, 2020. Transplant recipients were excluded from the initial safety studies of COVID-19 vaccines, and there was concern that transplant recipients may have suboptimal immunogenicity due to immunosuppression. Among solid organ transplant recipients who received the mRNA vaccines, investigators reported that an antibody response was found in only 14% to 17% after the first dose and 48% to 51% of transplant recipients after the second dose. 4,5 Although the study did report that COVID-19 vaccines appear to be safe in transplant recipients, the implications of only partial antibody response to vaccination toward protection from COVID-19-related morbidity and mortality remain unknown. 5 Therefore, we sought to assess the safety and effectiveness of COVID-19 vaccination in a large cohort of OHT recipients. IMPORTANCE Orthotopic heart transplant (OHT) recipients are at increased risk for morbidity and mortality after SARS-CoV-2 infection. Although antibody response to COVID-19 vaccination is lower in solid organ transplant recipients, there has been no study assessing the safety and effectiveness of COVID-19 vaccination in OHT recipients.OBJECTIVE To assess the safety and effectiveness of COVID-19 vaccination and associations with SARS-CoV-2 infection and clinical outcomes in a large population of adult OHT recipients.DESIGN, SETTING, AND PARTICIPANTS This case-control study examined data from a US heart transplant program at a single center for all adult recipients of OHT who were followed up

Background Hydrogen peroxide (H2O2) can be used in vitro to simulate oxidative stress. In retinal organ cultures, H2O2 induces strong neurodegeneration of the retina. It is known that oxidative stress plays a role in the development of several retinal diseases including glaucoma and ischemia. Thus, we investigated whether processes underlying oxidative stress can be prevented by hypothermia using an ex vivo organ culture model of porcine retinas. Methods Porcine retinal explants were cultivated for 5 and 8 days. Oxidative stress was induced via 300 μM H2O2 on day 1 for 3 hours. Hypothermia treatment at 30°C was applied simultaneously with H2O2, for 3 hours. Retinal ganglion cells (RGCs), apoptosis, bipolar and cholinergic amacrine cells, microglia and macroglia were evaluated immunohistologically. Apoptosis rate was additionally analysed via western blot. Results Reduced apoptosis rates through hypothermia led to a preservation of RGCs (P < .001). Amacrine cells were rescued after hypothermia treatment (P = .17), whereas bipolar cells were only protected partly. Additionally, at 8 days, microglial response due to oxidative stress was completely counteracted via hypothermia (P < .001). Conclusions H2O2 induced strong degenerative processes in porcine retinas. The role of oxidative stress in the progression of retinal diseases makes this ex vivo organ culture model suitable to investigate new therapeutic approaches. In the present study, the damaging effect of H2O2 to several retinal cell types was counteracted or strongly alleviated through hypothermia treatment. Especially RGCs, which are affected in glaucoma disease, were protected due to a reduced apoptosis rate through hypothermia.

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