Long-term kidney transplant recipients exhibit a dominance of T-lymphocyte subpopulations with an immunosenescent phenotype
Evangelos Memmos1, Georgios Lioulios2, Efstratios Kasimatis2, Aliki Xochelli3, Lambros Vagiotas4, Vasiliki Nikolaidou3, Nikolaos Antoniadis4, Georgios Tsoulfas4, Maria Stangou2, Asimina Fylaktou3.
1Nephrology Department, “Papageorgiou” General Hospital, Thessaloniki, Greece; 21st Nephrology Department, Aristotle University, Hippokration General Hospital, Thessaloniki, Greece; 3National Peripheral Histocompatibility Center and Immunology Department, Hippokration General Hospital, Thessaloniki, Greece; 4Department of Transplant Surgery, Aristotle University, Hippokration General Hospital, Thessaloniki, Greece
Introduction: Kidney transplantation (KTx) incurs significant alterations to the acquired cellular immunity. The purpose of this ongoing study was the evaluation of the impact of long-term KTx on the immunosenescent phenotype of T-lymphocytes.
Method: Total lymphocytes, CD4+, CD8+, Natural Killer (NK), CD4+CD28null, CD8+CD28null as well as CD4+CD25+FOXP3 (Tregs) T-cells were evaluated by flow cytometry in long–term patients who had received a transplant at least 17 years ago and in patients transplanted 1 year ago.
Results: The study population consisted of 25 long-term and 38 recently transplanted KT recipients. The two groups did not exhibit significant differences regarding patient age (p=0,714), eGFR (p=0,153), sex (p=0,304), compatible class I (p=0,496) and class II (p=0,334) HLA antigens, rejection (p=0,154) and DGF episodes (p=0,522), preemptive transplantations (p=0,092) and patients with a history of CMV infection (p=0,168). The percentage of patients with DSAs (4, 6,6% vs 0, 0% p=0,017), living donor transplants (16, 64% vs 15, 39,5%, p=0,049) and infection episodes (22, 88% vs 3, 7,9%, p<0,001) were higher in the long-term group, while patients treated with basiliximab (11, 57,9% vs. 35, 92,1%, p=0,004) and dialysis vintage (30:2-90, vs 75,5:0-156, p=0,028 ) were higher in the control group. Long-term KT recipients showed a significantly higher absolute count of total lymphocytes (2300: 1245-3900 /μL vs 1600: 800-2900 /μL, p=0,003), CD4+ (1266 ± 591 vs 781 ± 320/μL, p<0,001, CD4+CD28null (125: 26-2232/μL vs 41: 2-254/μL, p<0,001), and CD8+CD28null (441: 55-922/μL vs 241: 34-1601/μL, p=0,021) T-lymphocytes as well as a higher percentage of CD4+ T-cells (52,2 ± 13% vs 44,8 ± 11,6%, p=0,024) and a lower percentage of Tregs (2,8: 0-7,5% vs 4,2: 1,1-7,8%, p<0,0001). The percentage of total lymphocytes (p=0,183), CD8+ T-cells (p=0,171), NK cells (p=0,174), and the absolute count of NK cells (p=0,653) and Tregs (p=0923) did not differ between groups.
Conclusions: The preliminary results of our study show that long-term kidney transplant recipients are characterized by an increase in T-cell subpopulations with an immunosenescent phenotype, possibly explaining the low risk of rejection and high prevalence of cancer and infection in these patients.
