High Regulatory T-Cell Levels at 1 Year Posttransplantation Predict Long-Term Graft Survival Among Kidney Transplant Recipients

doi:10.1016/j.transproceed.2012.09.083

Transplantation Proceedings

Volume 44, Issue 9, November 2012, Pages 2538-2541

https://doi.org/10.1016/j.transproceed.2012.09.083 Get rights and content

Abstract

Introduction

Regulatory T cells (Tregs) have gained an important role in mechanisms of tolerance and protection against the transplant rejection. However, only limited retrospective data have shown a relationship between peripheral blood Tregs and better long-term graft survival. The purpose of the present study was to investigate prospectively circulating Treg levels and their association with long-term graft survival.

Methods

Ninety kidney transplant recipients underwent measurement of Treg levels in peripheral blood before as well as at 6 months and 1 year posttransplantation. Receiver operating characteristic curves were applied to test the sensitivity and specificity of Treg levels to predict prognosis.

Results

Treg levels before transplantation correlated with those at 6 months and 12 months posttransplantation (P < .001 and P = .002, respectively). Patients who maintained high Treg levels (above 70th percentile) at both 6 and 12 months displayed better long-term graft survival at 4 and 5 years follow-up (P = .04 and P = .043 respectively). There was no effect on patient survival.

Conclusion

Detection of high levels of peripheral blood Tregs was associated with better graft survival possibly using as a potential marker of prognosis.

Section snippets

Patients

From January 2005 90 consecutive KTR followed at our hospital were recruited for the study. All patients were informed about the study and gave written consent. The patients were monitored before as well as at 6 and 12 months posttransplantation. Their demographic, clinical, and main immunologic variables are summarized in Table 1.

Flow Cytometry

From 2005 to 2008, we identified Tregs as CD4⁺CD25^highFoxp3⁺. Upon description of low CD127 expression as a marker of Treg cells.⁸ Tregs were defined as CD4⁺CD25⁺CD127

Regulatory T Cells in Renal Transplant Patients

Peripheral blood Treg levels decreased significantly at 6 months recovering to basal levels at 1 year posttransplantation: mean ± standard deviation pretransplantation, 6 months and 1 year posttransplantation were 19.34 ± 18.91 cells/mm³, 13.97 ± 14.15 cells/mm³ and 17.27 ± 15.48 cells/mm³ respectively. The P values of Treg levels pretransplantation versus 6 months, 6 months versus 1 year, and pretransplantation versus 12 months were .0016, .0134, and .21 respectively. There was a good

Discussion

Contradictory evidence has been presented on the role of circulating Tregs as tolerance biomarkers in kidney transplantation. Whereas high Tregs levels in peripheral blood have been associated with COT in LTR,3, 4 no association has been observed in KTRs. However, for prospective studies have investigated the association of Treg levels with long-term graft survival.

A general decrease in Treg has been observed at 6 months posttransplantation.¹⁰ although a few patients maintain high levels at

Acknowledgments

The authors would like to thanks Iñaki Beares, Carolina Santacruz, and María San Martin for their helpful technical assistance.

References (11)

Y. Li et al.
Analyses of peripheral blood mononuclear cells in operational tolerance after pediatric living donor liver transplantation
Am J Transplant
(2004)
M. Martinez-Llordella et al.
Multiparameter immune profiling of operational tolerance in liver transplantation
Am J Transplant
(2007)
L. Liu et al.
Absolute of CD4(+)CD25(+)FOXP3(+) regulatory T-cell count rather than its ratio in peripheral blood is related to long-term survival of renal allografts
Transplant Proc
(2012)
Y.J. Lin et al.
Suppressive efficacy and proliferative capacity of human regulatory T cells in allogeneic and xenogeneic responses
Transplantation
(2008)
K.J. Wood et al.
Regulatory T cells in transplantation tolerance
Nat Rev Immunol
(2003)

There are more references available in the full text version of this article.

Cited by (20)

The relationship between T-cell infiltration in biopsy proven acute T-cell mediated rejection with allograft function and response to therapy: A retrospective study
2022, Transplant Immunology
Citation Excerpt :
In some studies, levels of FOXP3 T cells in blood and association with long-term survival in 90 patients were analyzed. High FOXP3s level associated with better short and long-term survival [16]. Several studies had shown the role of T regs otherwise.
To evaluate the degree of CD3, CD20, Th17, and Tregs infiltration in kidney biopsy of the patients with acute cellular rejection and the possible relation with graft outcome.
In this retrospective study, fifty patients with Acute T Cell-Mediated Rejection (ATCMR) were enrolled. Previous and one year clinical follow-up data were collected. The kidney specimens were evaluated for infiltration of CD3, CD20, FOXP3, and Th17 with IHC. According to the serum creatinine level in one-year follow-up of the patients after rejection therapy and function of the transplanted organ from the day admitted into the hospital, they were respectively categorized in Stable graft function versus impaired graft function; appropriate response to treatment versus failure to response.
Treg (P = 0.96) and Th17 (P = 0.24) cells were more in the unstable group than the stable group, but the difference wasn't significant. On the other hand, the FOXP3/Th17 ratio was higher in the stable group (P = 0.22). Moreover Treg (P = 0.1) and Th17 (P = 0.15) were higher in failure to response group, but FOXP3/Th17 was higher in proper response group (P = 0.8).
From the results, it can be concluded that TH17 infiltration has a more significant effect on graft outcome and response to rejection therapy.
Immune Profiling of Peripheral Blood Mononuclear Cells at Pancreas Acute Rejection Episodes in Kidney-Pancreas Transplant Recipients
2022, Transplant International
Therapeutic Opportunities for Immunoreceptor-Engineered T Cell Therapy for Modulation of Alloimmunity
2022, Journal of Immunology
Effect of panel reactive antibodies on T cell immunity reinstatement following renal transplantation
2022, World Journal of Transplantation
Uncover diagnostic immunity/hypoxia/ferroptosis/epithelial mesenchymal transformation-related CCR5, CD86, CD8A, ITGAM, and PTPRC in kidney transplantation patients with allograft rejection
2022, Renal Failure
Effects of Desflurane and Sevoflurane anesthesia on regulatory T cells in patients undergoing living donor kidney transplantation: A randomized intervention trial
2020, BMC Anesthesiology

View all citing articles on Scopus

: This work was partially supported by grants of Fondo Investigaciones Sanitarias-ISCIII (PI1100990 and REDINREN) and Fundación Marqués de Valdecilla-IFIMAV (API 11/24).

: M.A. and M.L.-H. contributed equally in the work.

View full text

2nd congress of the Spanish transplantation societyKidney transplantation: OutcomesHigh Regulatory T-Cell Levels at 1 Year Posttransplantation Predict Long-Term Graft Survival Among Kidney Transplant Recipients

Abstract

Introduction

Methods

Results

Conclusion

Section snippets

Patients

Flow Cytometry

Regulatory T Cells in Renal Transplant Patients

Discussion

Acknowledgments

Am J Transplant

Am J Transplant

Transplant Proc

Suppressive efficacy and proliferative capacity of human regulatory T cells in allogeneic and xenogeneic responses

Transplantation

Regulatory T cells in transplantation tolerance

Nat Rev Immunol

2nd congress of the Spanish transplantation society
Kidney transplantation: Outcomes
High Regulatory T-Cell Levels at 1 Year Posttransplantation Predict Long-Term Graft Survival Among Kidney Transplant Recipients