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

Background Cardiac transplantation is a limited option for end-stage heart failure because of the shortage of donor organs. Left-ventricular assist de vices (LVADs) are currently under investigation as permanent therapy for en d-stage heart failure, but long-term successful device implantation is limi ted because of a high rate of serious infections. To examine the relation b etween LVAD-related infection and host immunity, we investigated immune res ponses in LVAD recipients. Methods We compared the rate of candidal infection in 78 patients with New York Heart Association class IV heart failure who received either an LVAD ( n=40) or medical management (controls, n=38). Fluorochrome-labelled monoclo nal antibodies were used in analyses of T-cell phenotype. Analysis of T-cel l function included intradermal responses to recall antigens and proliferat ive responses after stimulation by phytohaemagglutinin, monoclonal antibodi es to CD3, and mixed lymphocyte culture. We measured T-cell apoptosis in vi vo by annexin V binding, and confirmed the result by assessment of DNA frag mentation. Activation-induced T-cell death was measured after T-cell stimul ation with antibodies to CD3. All immunological tests were done at least 1 month after LVAD implantation. Between-group comparisons were by Kaplan-Mei er actuarial analysis and Students t test. Findings By 3 months after implantation of LVAD, the risk of developing can didal infection was 28% in LVAD recipients, compared with 3% in controls (p =0.003). LVAD recipients had cutaneous anergy to recall antigens and lower (<70%) T-cell proliferative responses than controls after activation via th e T-cell receptor complex (p<0.001). T cells from LVAD recipients had highe r surface expression of CD95 (Fas) (p<0.001) and a higher rate of spontaneo us apoptosis (p<0.001) than controls. Moreover, after stimulation with anti bodies to CD3, CD4 T-cell death increased by 3.2-fold in LVAD recipients co mpared with only 1.2-fold in controls (p<0.05). Interpretation LVAD implantation results in an aberrant state of T-cell act ivation, heightened susceptibility of CD4 T cells to activation-induced cel l death, progressive defects in cellular immunity, and increased risk of op portunistic infection.