ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: SA-PO996

Impaired T Cell Functionality in ESRD Is Not Reversed by Immune Checkpoint Blockade

Session Information

Category: Dialysis

  • 701 Dialysis: Hemodialysis and Frequent Dialysis

Authors

  • Chiu, Yen-Ling, Far Eastern Memorial Hospital, Banciao, New Taipei City, Taiwan
  • Lay, Fang-Yun, Far Eastern Memorial Hospital, Banciao, New Taipei City, Taiwan
  • Pan, Szu-Yu, Far Eastern Memorial Hospital, Banciao, New Taipei City, Taiwan
  • Shu, Kai-Hsiang, National Taiwan University, Taipei, Taiwan
Background

Polyfunctional T cells are critical for maintaining protection against pathogens. Patients with end-stage renal disease (ESRD) are at increased risks for infection but their pathogen-specific T cell function is not well understood.

Methods

32 healthy individuals and 57 patients on maintenance hemodialysis were enrolled in this study. All the donors were seropositive for CMV. In addition to PMA/ionomycin, CMV peptide pools (IE1 and pp65) were used to stimulate PBMCs and four effector functions were measured by multicolor flow cytometry (IL-2, TNFα, IFNγ and CD107a) to identify polyfunctional T cells (cells capable of all four functions). The statistical comparisons were performed using the Kruskal-Wallis equality-of-populations rank test.

Results

The age of the two groups was similar (mean, 60 years old). ESRD patients showed increased levels of T cell differentiation, including the decrease in CD4+ and CD8+ TN cells and the increase in the CD4+ and CD8+ TEM and TEMRA cells. T cells from ESRD patients exhibited significant impairment in their effector functions in response to PMA/ionomycin, and such impairment is independent from differentiation status. While the cellular frequency of virus-reactive CD4+ and CD8+ T cells were similar, polyfunctional T cell response were dramatically reduced in the ESRD. The CD8+ CMV-pp65-reactive polyfunctional cell frequencies showed the most dramatic reduction, 12.4% in healthy donors versus 0.8% in ESRD patients (p<0.001). We further identified that immune checkpoint molecules PD-1 and TIM-3 are upregulated on T cells from ESRD patients; nevertheless, immune checkpoint blockade therapy and regulatory T cell depletion did not reverse the dysfunction phenotype. Transcriptome analysis demonstrated pathway enrichment of advanced T cell differentiation in ESRD but did not demonstrate the enrichment of exhaustion related genes in T cells from ESRD patients.

Conclusion

Renal failure patients are characterized by a dramatic loss of polyfunctional T cells and impairment in T cell effector functions, which might explain the increased risk for infection and cancer. Although inhibitory receptors such as PD-1 are upregulated, such phenomenon is distinct from T cell exhaustion.

Funding

  • Government Support - Non-U.S.