Quantitative changes in T-cell populations after left ventricular assist device implantation - Relationship to T-cell apoptosis and soluble CD95

Background-Left ventricular assist devices (LVADs) are currently being eval uated as permanent therapy for end-stage heart failure. Because life-threat ening infections limit successful long-term device implantation, we investi gated the relationship between quantitative T-cell defects in LVAD recipien ts and CD95-mediated T-cell apoptosis. Methods and Results-Immunological studies were performed in NYHA class TV p atients awaiting cardiac transplantation who received either a TCI Heartmat e left ventricular assist device (LVAD) or medical management. Fluorochrome -labeled Mabs were used in T-cell phenotypic analyses. T-cell apoptosis was measured by annexin V binding of T cells cultured in medium for 24 hours. Circulating serum levels of soluble CD95 were measured by ELISA. LVAD recip ients had a relative lymphopenia and reduction in CD4 T-cell levels compare d with NYHA class IV heart failure controls. These observations were confir med in a longitudinal study in LVAD recipients, which showed that device im plantation was accompanied by progressive and sustained reductions in circu lating CD4 T-cell levels. These abnormalities in LVAD recipients were accom panied by increased levels of circulating soluble CD95 and by excessive CD4 and CD8 T-cell apoptosis. Susceptibility to induction of apoptosis was >2- fold greater for CD4 T cells than for CD8 T cells. Conclusions-These results suggest that the reduction in CD4 T-cell levels a ccompanying LVAD implantation is a consequence of an augmented pathway of C D95-mediated apoptosis, The clinical consequences of these abnormalities ma y include increased prevalence of systemic infections.