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

Lancet. 1999 Aug 14;354(9178):550-5. doi: 10.1016/s0140-6736(98)10359-8.


Background: Cardiac transplantation is a limited option for end-stage heart failure because of the shortage of donor organs. Left-ventricular assist devices (LVADs) are currently under investigation as permanent therapy for end-stage heart failure, but long-term successful device implantation is limited because of a high rate of serious infections. To examine the relation between LVAD-related infection and host immunity, we investigated immune responses 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 monoclonal antibodies were used in analyses of T-cell phenotype. Analysis of T-cell function included intradermal responses to recall antigens and proliferative responses after stimulation by phytohaemagglutinin, monoclonal antibodies to CD3, and mixed lymphocyte culture. We measured T-cell apoptosis in vivo by annexin V binding, and confirmed the result by assessment of DNA fragmentation. Activation-induced T-cell death was measured after T-cell stimulation with antibodies to CD3. All immunological tests were done at least 1 month after LVAD implantation. Between-group comparisons were by Kaplan-Meier actuarial analysis and Student's t test.

Findings: By 3 months after implantation of LVAD, the risk of developing candidal 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 the T-cell receptor complex (p<0.001). T cells from LVAD recipients had higher surface expression of CD95 (Fas) (p<0.001) and a higher rate of spontaneous apoptosis (p<0.001) than controls. Moreover, after stimulation with antibodies to CD3, CD4 T-cell death increased by 3.2-fold in LVAD recipients compared with only 1.2-fold in controls (p<0.05).

Interpretation: LVAD implantation results in an aberrant state of T-cell activation, heightened susceptibility of CD4 T cells to activation-induced cell death, progressive defects in cellular immunity, and increased risk of opportunistic infection.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Apoptosis
  • Candidiasis / epidemiology
  • Candidiasis / etiology*
  • Cell Death
  • Female
  • Flow Cytometry
  • Heart Failure / complications
  • Heart Failure / immunology*
  • Heart Failure / surgery*
  • Heart-Assist Devices / adverse effects*
  • Heart-Assist Devices / microbiology
  • Humans
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Risk Factors
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*