{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T10:36:24Z","timestamp":1773311784888,"version":"3.50.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Despite the growing number of elderly kidney transplant (Ktx) recipients, few studies have examined the effects of immunosuppression on their lymphocyte profiles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We evaluated the early conversion from mycophenolate sodium (MPS) to everolimus (EVL) after rabbit antithymocyte globulin (rATG) 2 mg\/kg induction in elderly kidney recipients. Three groups of KTx patients were compared: (a) Young (n=20, 36 \u00b1 7 y) receiving standard immunosuppression (Group A1) (prednisone, tacrolimus, and MPS), (b) Elderly (n=35, 65 \u00b1 3 y) receiving standard immunosuppression (Group B1), and (c) Elderly (n=16, 65 \u00b1 3 y) with early (mean 30 d) conversion from MPS to EVL (Group B2). Naive, memory, and regulatory peripheral blood TCD4<jats:sup>+<\/jats:sup> lymphocytes were quantified at 0, 30, and 365 d.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Results are reported as [mean(p25\u2013p75)]. Young recipients had higher lymphocyte counts at baseline [2,100(1,630\u20132,400) vs. 1,310 (1,000\u20131,600)\/mm<jats:sup>3<\/jats:sup>, p&amp;lt;0.0001] maintained higher counts within 365 d [1,850(1,590\u20132,120) vs. 1,130(460\u20131,325)\/mm<jats:sup>3<\/jats:sup>, p=0.018 and vs. 1,410(805\u20131,895)\/mm<jats:sup>3<\/jats:sup>, p=0.268]. Elderly recipients showed a decrease in lymphocytes within 30 d [1,310(1,000\u20131,600) vs. 910(700\u20131,198)\/mm<jats:sup>3<\/jats:sup>, p=0.0012] with recovery within 365 d. The same pattern was observed in total lymphocytes and TCD4<jats:sup>+<\/jats:sup> counts. Rabbit antithymocyte globulin induced a reduction in central memory T-cell percentages at 30 d in both young recipients [6.2(3.77\u201310.8) vs. 5.32(2.49\u20137.28)% of CD4<jats:sup>+<\/jats:sup>, p=0.036] and in elderly recipients [8.17(5.28\u201312.88) vs. 6.74(4.36\u201311)% of CD4<jats:sup>+<\/jats:sup>, p=0.05] on standard immunosuppression, returning to baseline at 365 d in elderly recipients but not in young recipients. Regulatory T CD39<jats:sup>+<\/jats:sup> cells (Treg) percentages decreased at 30 d in elderly recipients [2.1(1.23\u20133.51) vs. 1.69(0.8\u20132.66)% of CD4<jats:sup>+<\/jats:sup>, p=0.0028] and in young recipients [1.29(0.45\u20131.85) vs. 0.84(0.18\u20131.82)% of CD4<jats:sup>+<\/jats:sup>, p=0.0038], returning to baseline at 365 d in elderly recipients [2.1(1.23\u20133.51) vs. 2.042(0.88\u20132.42)% of CD4<jats:sup>+<\/jats:sup>], but not in young recipients [1.29(0.45\u20131.85) vs. 0.86(0.7\u20131.34) % of CD4<jats:sup>+<\/jats:sup>]. The elderly everolimus conversion group did not show significant changes in cell profile over time or compared to elderly recipients with standard immunosuppression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p>nEverOld Trial, identifier NTC01631058.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1405855","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T04:22:22Z","timestamp":1726806142000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of two immunosuppression regimens on T-lymphocyte subsets in elderly kidney transplant recipients"],"prefix":"10.3389","volume":"15","author":[{"given":"Geraldo Rubens R.","family":"Freitas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria da Luz","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiana","family":"Agena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francine B. C.","family":"Lemos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavio J. de","family":"Paula","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ver\u00f4nica","family":"Coelho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elias","family":"David-Neto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelson Z.","family":"Galante","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.0590041539.x","article-title":"Exponentially increased risk of infectious death in older renal transplant recipients","volume":"59","author":"Meier-Kriesche","year":"2001","journal-title":"Kidney Int"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.458","article-title":"Malignancy-related mortality following kidney transplantation is common","volume":"85","author":"Farrugia","year":"2014","journal-title":"Kidney Int"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000275423.69689.dc","article-title":"Immunosuppression of the elderly kidney transplant recipient","volume":"84","author":"Danovitch","year":"2007","journal-title":"Transplantation"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.2165\/00002512-200118100-00004","article-title":"Immunosuppression in elderly renal transplant recipients: are current regimens too aggressive","volume":"18","author":"Meier-Kriesche","year":"2001","journal-title":"Drugs Aging"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2011.03686.x","article-title":"Systematic review: kidney transplantation compared with dialysis in clinically relevant outcomes","volume":"11","author":"Tonelli","year":"2011","journal-title":"Am J Transplant"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2018010009","article-title":"Everolimus with reduced calcineurin inhibitor exposure in renal transplantation","volume":"29","author":"Pascual","year":"2018","journal-title":"J Am Soc Nephrol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1111\/j.1432-2277.2012.01465.x","article-title":"Everolimus plus early tacrolimus minimization: a phase III, randomized, open-label, multicentre trial in renal transplantation","volume":"25","author":"Langer","year":"2012","journal-title":"Transpl Int"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1506027","article-title":"Belatacept and long-term outcomes in kidney transplantation","volume":"374","author":"Vincenti","year":"2016","journal-title":"N Engl J Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1506027","article-title":"Reduced exposure to calcineurin inhibitors in renal transplantation","volume":"357","author":"Ekberg","year":"2007","journal-title":"N Engl J Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001369","article-title":"Longitudinal pharmacokinetics of tacrolimus in elderly compared with younger recipients in the first 6 months after renal transplantation","volume":"101","author":"David-Neto","year":"2017","journal-title":"Transplantation"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001549","article-title":"Longitudinal pharmacokinetics of everolimus when combined with low-level of tacrolimus in elderly renal transplant recipients","volume":"101","author":"David-Neto","year":"2017","journal-title":"Transplantation"},{"key":"B12","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1111\/j.1600-6143.2009.02834.x","article-title":"KDIGO clinical practice guideline for the care of kidney transplant recipients","year":"2009","journal-title":"Am J Transplant"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.07540810","article-title":"Induction immunosuppressive therapy in the elderly kidney transplant recipient in the United States","volume":"6","author":"Gill","year":"2011","journal-title":"Clin J Am Soc Nephrol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016070768","article-title":"Comparing outcomes between antibody induction therapies in kidney transplantation","volume":"28","author":"Koyawala","year":"2017","journal-title":"J Am Soc Nephrol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD003897.pub3","article-title":"Interleukin 2 receptor antagonists for kidney transplant recipients","volume":"1","author":"Webster","year":"2010","journal-title":"Cochrane Database Syst Rev"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa060068","article-title":"Thymoglobulin Induction Study Group. 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