Activation-induced T-cell death and immune dysfunction after implantation of left-ventricular assist de vice

Nonvalvular Cardiovascular Device–Related Infections

“…25 In addition, T-cell function may be influenced by the presence of some of these devices. 26 Endothelialization of an implanted device is a key factor in the prevention of subsequent infection. In animal studies of explanted devices, endothelialization has been noted to occur as early as 1 month after implantation and to be complete by 3 months.…”

Intravenous Pulse Administration of Cyclophosphamide Is an Effective and Safe Treatment for Sensitized Cardiac Allograft Recipients

“…Moreover, because a high rate of fungal infection in LVAD recipients seems to be attributable to progressive defects in cellular immunity attributable to excessive CD4 T-cell activation and apoptosis, the notable lack of infections in such patients treated with cyclophosphamide might be a result of the drug's effect on cycling CD4 T cells. 8 The intravenous cyclophosphamide regimen used in our study was adapted from protocols used in the treatment of SLE and systemic vasculitides, where intermittent low-dose pulse therapy has been shown to significantly reduce the incidence of complications compared with oral cyclophosphamide while maintaining efficacy. 18 -20 The sustained efficacy of intermittent intravenous pulses of cyclophosphamide compared with daily oral use may be attributable to the high peak dose after each intravenous administration, whereas the reduced short-term toxicity of the regimen lies in the reduction of cumulative dose, with adequate interdose interval allowing for bone marrow recovery.…”

“…Whereas alloreactivity in retransplant candidates, recipients of blood products, and multiparous women is a result of repeated Band T-cell exposure to alloantigens, the high frequency of alloreactivity in LVAD recipients 6,7 seems to additionally result from polyclonal B-cell activation attributable to selective loss of Th1-type T cells through activation-induced cell death and unopposed production of Th2-type cytokines. 8 Previous interventions in sensitized recipients have focused on therapies aimed predominantly at immunoglobulin depletion and B-cell suppression, including plasmapharesis, 9 immunoadsorption, 10 or intravenous immune globulin (IVIg). 11,12 Because these therapies do not directly impact CD4 T-cell alloreactivity, immunoglobulin-depleting regimens have not demonstrated beneficial effects on rejection or graft survival in sensitized recipients.…”

Peripheral Blood Mononuclear Cell Secretome for Tissue Repair

“…Apoptotic lymphocytes are known to play important roles in the pathophysiology of several chronic inflammatory diseases and are elevated following implantation of left-ventricular assistance devices [44] or heart transplantation [45] and during hemodialysis [46,47], sepsis [48][49][50], COPD, and asthma (reviewed in [51]). Thus, from this historic data set multiple pathological disease entities related to augmented initiation of apoptosis in PBMCs in the immune system can be deduced.…”