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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Alloimmunity and Transplantation
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1405855
Effects of two immunosuppression regimens on T lymphocyte subsets in elderly kidney transplant recipients
Provisionally accepted- 1 Hospital Universitário de Brasília, Brasília, Brazil
- 2 Brazilian Hospital Services Company, Natal, Brazil
- 3 University of São Paulo, São Paulo, Rio Grande do Sul, Brazil
- 4 Heart Institute, Clinical Hospital, Faculty of Medicine, University of São Paulo, São Paulo, Brazil
- 5 Instituto de Investigação em Imunologia, Instituto Nacional de Ciência e Tecnologia (iii-INCT), São Paulo, São Paulo, Brazil
- 6 Laboratório de Investigação Médica em Imunologia LIM 48 do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
Despite the growing number of elderly kidney transplant(Ktx) recipients, few studies have examined the effects of immunosuppression on their lymphocyte profiles. METHODS: We evaluated the early conversion from mycophenolate sodium (MPS) to everolimus (EVL) after rabbit antithymocyte globulin (rATG) 2mg/Kg induction in elderly kidney recipients. Three groups of KTx patients were compared: (a)Young (n=20, 36±7y) receiving standard immunosuppression (GROUP A1) (prednisone, tacrolimus and MPS), (b) Elderly (n=35, 65±3y) receiving standard immunosuppression (GROUP B1) and (c) Elderly (n=16, 65±3y) with early (mean 30 days) conversion from MPS to EVL (GROUP B2). Naïve, memory and regulatory peripheral blood TCD4+ lymphocytes were quantified at 0, 30and 365days(d). Results are reported as [mean(p25-p75)]. Young recipients had higher lymphocyte counts at baseline [2100(1630-2400) vs 1310(1000-1600)/mm3, p<0.0001] maintained higher counts within 365d [1850(1590-2120) vs 1130(460-1325)/mm3, p=0.018 and vs. 1410(805-1895)/mm3, p=0.268]. Elderly recipients showed decrease in lymphocytes within 30d[1310(1000-1600) vs 910(700-1198)/mm3, p=0.0012] with recovery within 365d. The same pattern was observed in total lymphocytes and TCD4+ counts. Rabbit antithymocyte globulin induced a reduction in central memory T-cell percentages at 30 days in both young recipients [6.2(3.77-10.8) vs 5.32(2.49-7.28)% of CD4+, p=0.036] and in elderly recipients [8.17(5.28-12.88) vs 6.74(4.36-11)% of CD4+, p=0.05] on standard immunosuppression, returning to baseline at 365 days in elderly recipients but not in young recipients. Regulatory T CD39+cells(TREG) percentages decreased at 30d in elderly recipients [2.1(1.23-3.51) vs 1.69(0.8-2.66)% of CD4+, p=0.0028] and in young recipients [1.29(0.45-1.85) vs 0.84(0.18-1.82)% of CD4+, p=0.0038], returning to baseline at 365 days in elderly recipients [2.1(1.23-3.51) vs 2.042(0.88-2.42)% of CD4+], but not in young recipients [1.29(0.45-1.85) vs 0.86(0.7-1.34) % of CD4+]. The elderly everolimus conversion group did not show significant changes in cell profile over time nor compared to elderly recipients with standard immunosuppression. Aging favored the maintenance of TREG during the late transplantation period despite ongoing immunosuppression. Lymphocyte depletion due to rATG was more prominent in elderly recipients and affected memory subsets with a temporary reduction in central memory T-cells. However, conversion to everolimus did not impact TREG profile. Reducing the dose of rATG in elderly recipients seems necessary for the expected lymphocyte changes with EVL to occur.
Keywords: regulatory (Treg) cell, kidney tranplantation, memory T CD4 + cells, Elderly, Everolimus
Received: 24 Mar 2024; Accepted: 06 Aug 2024.
Copyright: © 2024 Freitas, Fernandes, Agena, Lemos, Paula, Coelho, David-Neto and Galante. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Nelson Z. Galante, University of São Paulo, São Paulo, Rio Grande do Sul, Brazil
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Maria da Luz Fernandes
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