Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 10 04 1 13 Zahra Rasouli Department of Biological Sciences, Faculty of Engineering and Science, Science and Arts University, Yazd, Iran Maryam Rahimi Foroudi Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Afsoon Afshari Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Amaneh Javid Department of Biological Sciences, Faculty of Engineering and Science, Science and Arts University, Yazd, Iran Seyed Mohsen Miresmaeili Department of Biology, Science and Arts University, Yazd, Iran Mahdi Golshan Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Ramin Yaghobi Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran 2026 02 28 2026 07 19 BK polyomavirus (BKPyV) reactivation is a major cause of allograft dysfunction and BKPyV-associated nephropathy (BKPyVAN) in kidney transplant recipients (KTRs). Although CD4⁺ T-cell responses are considered important for viral control, the immunomodulatory effects of BKPyV small T antigen (ST-Ag) remain poorly understood. This study investigated the effects of ST-Ag alone and combined large T antigen (LT-Ag)/ST-Ag stimulation on CD4⁺ T-cell differentiation and function in KTRs. Peripheral blood mononuclear cells (PBMCs) from 10 KTRs and five healthy controls were stimulated with ST-Ag alone or a combined LT-Ag/ST-Ag peptide pool. Naive, central memory, and effector memory CD4⁺ T-cell subsets were analyzed by flow cytometry using CCR7, CD45RO, CD107a, and granzyme B. Expression of T-bet, GATA3, STAT3, STAT6, and perforin was quantified by real-time PCR. Combined LT-Ag/ST-Ag stimulation was associated with a higher frequency of naive CD4⁺ T cells and lower frequencies of central and effector memory subsets in BKPyV-reactivated KTRs compared with BKPyV-negative recipients. Expression of T-bet, GATA3, STAT3, and STAT6 was significantly reduced, whereas perforin expression was increased. These findings are consistent with altered CD4⁺ T-cell differentiation in BKPyV-reactivated recipients. BKPyV ST-Ag may contribute to altered CD4⁺ T-cell differentiation and immune dysregulation during viral reactivation. These findings provide preliminary insight into immune alterations associated with BKPyV reactivation and warrant validation in larger, independent cohorts. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4769 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4769/2429