Apoptosis of Peripheral CD4⁺ T-Lymphocytes in End-Stage Renal Disease Patients Under Hemodialysis and rhEPO Therapies

Abstract

End-stage renal disease (ESRD) under hemodialyses (HD) is related with a higher propensity to infections, essentially due to T-cell lymphopenia. We postulated that HD procedure affects CD4⁺ T cells, especially by inducing apoptotic death and that recombinant human erythropoietin (rhEPO) therapy may also play an important role in the modulation of the immune system in these patients. T-cell phenotype and apoptosis of HD patients and healthy controls were evaluated by flow cytometry using anticoagulated whole-blood samples. In 12 HD patients, these parameters were also analyzed before and immediately after HD procedure. HD patients showed a decrease in total circulating CD3⁺ lymphocytes, especially in CD4⁺ T cells (0.747 ± 0.410 vs. 0.941 ± 0.216 × 10⁹/L, p < 0.05), which could be a consequence of the higher proportion of CD3⁺ and CD4⁺ lymphocytes in the latest stage of apoptosis (or death) and of the higher proportion of apoptotic CD4⁺ T cells observed in the patients immediately after HD procedure (2.91 ± 0.780 vs. 3.90 ± 1.96, p < 0.05). A positive and statistically significant correlation between CD3⁺ and CD4⁺ lymphocytes in latest stage of apoptosis (or death) with HD time was found (CD3⁺: r = 0.592, p < 0.01; CD4⁺: r = 0.501, p < 0.01). We also found a negative and significant correlation between weekly rhEPO doses and the number of CD4⁺ T cells (r = –0.358, p < 0.05). In conclusion, HD procedure still contributes to the development of T-cell lymphopenia, at least in part, by apoptosis induction. It was also shown that rhEPO therapy is associated with the CD4⁺ T-cell decline, possibly by immune modulation, eliminating atypical cells and helping to restore the CD4⁺ T-cell subset.

• end-stage renal disease
• hemodialysis
• T-cell lymphopenia
• rhEPO therapy
• CD4⁺ T cells
• apoptosis

Acknowledgments

This work was supported by the “Fundação Portuguesa para a Ciência e Tecnologia” Project PIC/IC/83221/2007.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.