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Increased Frequency of Terminally Differentiated and Exhausted CD8+ T Cells Is Associated With Adverse Clinical Outcome After Mechanical Circulatory Support Device Implantation

J. Schaenman,1 Y. Korin,2 T. Sidwell,2 G. Sunga,2 G. Bondar,3 N. Wisniewski,3 M. Kwon,4 M. Cadeiras,3 M. Deng,3 E. Reed.2

1Medicine/Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA
2Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA
3Medicine/Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA
4Cardiothoracic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA.

Meeting: 2015 American Transplant Congress

Abstract number: D277

Keywords: Heart assist devices, Monitoring, T cells, Ventricular assist devices

Session Information

Session Name: Poster Session D: Late Breaking

Session Type: Poster Session

Date: Tuesday, May 5, 2015

Session Time: 5:30pm-6:30pm

 Presentation Time: 5:30pm-6:30pm

Location: Exhibit Hall E

Clinical outcomes vary after mechanical circulatory support device (MCSD) implantation, with some patients developing multi organ system dysfunction (MOD), sometimes leading to death. We hypothesized that increased frequency in terminally differentiated (TEMRA) and exhausted CD8+ T cells would be seen in patients with increased Model of End-Stage Liver Disease (MELD) score or death.

Methods: Peripheral blood mononuclear cells were isolated from 24 patients ages 25-81 pre- and post-MCSD placement. Immune phenotyping was performed by flow cytometry. Statistical analysis used linear regression for numeric variables and by Kruskal-Wallis test for categorical variables.

Results: Frequency of TEMRA cells significantly correlated with MELD (p=0.005) while frequency of naïve cells (CCR7+/CD45RA+) was inversely associated (p<0.001). Increased frequency of naïve CD8+ cells was associated with lower level of heart failure by INTERMACS score and younger patient age (both p<0.001). Increased frequency of the marker of exhaustion KLRG-1 was also associated with increased MELD score (p<0.001), and increased frequency of KLRG-1+ and programmed cell death (PD-1)+ T cells was associated with both MELD score (p<0.001) and death (p=0.022). Analysis of Sequential Organ Failure Assessment score as an alternate clinical marker showed similar findings.

Conclusion: Increase in T cell terminal differentiation and exhaustion is associated with increased MELD score and death after MCSD implantation, suggesting that immune dysfunction is part of the underlying mechanism leading to MOD. This data suggests the noninvasive monitoring of peripheral blood can be utilized to improve candidate selection and post-implant surveillance.

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To cite this abstract in AMA style:

Schaenman J, Korin Y, Sidwell T, Sunga G, Bondar G, Wisniewski N, Kwon M, Cadeiras M, Deng M, Reed E. Increased Frequency of Terminally Differentiated and Exhausted CD8+ T Cells Is Associated With Adverse Clinical Outcome After Mechanical Circulatory Support Device Implantation [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/increased-frequency-of-terminally-differentiated-and-exhausted-cd8-t-cells-is-associated-with-adverse-clinical-outcome-after-mechanical-circulatory-support-device-implantation/. Accessed May 19, 2025.

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