{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T06:24:17Z","timestamp":1787639057154,"version":"build-2736575974"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["K12AR084223"],"award-info":[{"award-number":["K12AR084223"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["U01 AG009740"],"award-info":[{"award-number":["U01 AG009740"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging"],"abstract":"\n Background<\/jats:title>\n Chronic kidney disease (CKD) is characterized by chronic inflammation and immune dysregulation. Aging of the adaptive immune system, marked by a shift from na\u00efve to memory T-cell phenotypes, is associated with systemic \u201cinflammaging\u201d, but sex-specific associations between these immunophenotypes and kidney function in older adults remain poorly understood.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We analyzed cross-sectional data from 8,970 participants (aged \u226556 years) in the 2016 Health and Retirement Study (HRS) Venous Blood Study. Seventeen adaptive immune cell subsets were quantified using multiparameter flow cytometry. Kidney function was assessed using estimated glomerular filtration rate (eGFR, mL\/min\/1.73\u00a0m\n 2<\/jats:sup>\n ) calculated from the 2021 race-free CKD-EPI creatinine-cystatin C equation. Survey-weighted linear regression models were adjusted for age, race\/ethnicity, education, body-mass index (BMI), clinical comorbidities (diabetes, elevated blood pressure\/hypertension), alcohol use, smoking status, and cytomegalovirus (CMV) serostatus. Sex-stratified analyses were conducted\n a priori<\/jats:italic>\n , and sex interaction terms were evaluated to assess effect modification.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Females were older and more likely to be never smokers, CMV seropositive, and have lower eGFR, whereas males were more likely to use alcohol, smoke, have diabetes, elevated blood pressure\/hypertension and higher educational attainment. In sex-stratified models, higher CD4\n +<\/jats:sup>\n T cells (\u03b2 = 0.96, P\n FDR<\/jats:sub>\n = 0.010), CD8\n +<\/jats:sup>\n na\u00efve T cells (\u03b2 = 0.87, P\n FDR<\/jats:sub>\n = 0.026), Ratio of CD4\n +<\/jats:sup>\n to CD8\n +<\/jats:sup>\n T cells (\u03b2 = 0.73, P\n FDR<\/jats:sub>\n = 0.036), and lymphocytes (\u03b2 = 2.42, P\n FDR<\/jats:sub>\n &lt;0.001) were associated with higher eGFR (higher kidney function) in females, while higher CD4\n +<\/jats:sup>\n effector memory T cells (Tem; \u03b2 = \u22121.58, P\n FDR<\/jats:sub>\n = 0.010), CD8\n +<\/jats:sup>\n effector T cells (Teff; \u03b2 = \u22121.00, P\n FDR<\/jats:sub>\n = 0.004), and CD8\n +<\/jats:sup>\n Tem (\u03b2 = \u22121.40, P\n FDR<\/jats:sub>\n = 0.002) were associated with lower eGFR (lower kidney function). In males, higher IgD + memory B cells (\u03b2 = 1.01, P\n FDR<\/jats:sub>\n = 0.005), IgD\u2212 memory B cells (\u03b2 = 1.04, P\n FDR<\/jats:sub>\n = 0.011), and lymphocytes (\u03b2 = 2.08, P\n FDR<\/jats:sub>\n &lt;0.001) were associated with higher eGFR. Significant sex interaction was observed for CD8\n +<\/jats:sup>\n Tem (P\n FDR<\/jats:sub>\n = 0.015), with a nominal interaction for CD8\n +<\/jats:sup>\n Teff (P\n FDR<\/jats:sub>\n = 0.060). Associations were similar in sensitivity analyses and were not modified by CMV serostatus.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Findings suggest that CD8\n +<\/jats:sup>\n Tem and Teff T cells may serve as sex-specific biomarkers of renal vulnerability in postmenopausal females and underscore the need for longitudinal and mechanistic studies to clarify underlying pathways.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fragi.2026.1882462","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:36:01Z","timestamp":1787636161000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Adaptive immune cells and kidney function in older adults: sex-specific associations in the health and retirement study (HRS)"],"prefix":"10.3389","volume":"7","author":[{"given":"Shannon M.","family":"Sullivan","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota","place":["Minneapolis, MN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bibin","family":"Joseph","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota","place":["Minneapolis, MN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shweta","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota","place":["Minneapolis, MN, United States"]},{"name":"Division of Epidemiology, School of Public Health, University of Minnesota","place":["Minneapolis, MN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihua","family":"Guan","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Health Data Sciences, School of Public Health, University of Minnesota","place":["Minneapolis, MN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy B.","family":"Karger","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota","place":["Minneapolis, MN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Faul","sequence":"additional","affiliation":[{"name":"Survey Research Center, Institute for Social Research, University of Michigan","place":["Ann Arbor, MI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharat","family":"Thyagarajan","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota","place":["Minneapolis, MN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"00257\u20133","DOI":"10.1016\/j.tips.2025.11.003","article-title":"Targeting androgen receptor signaling to enhance cancer immunotherapy","author":"Bader","year":"2025","journal-title":"Trends Pharmacol. 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