Impaired CD4+ Cytotoxic T Lymphocyte Activity in Polyomavirus BK Infected Kidney Transplant Recipients

Nasrin Noshadi; Ramin Yaghobi; Afsoon Afshari; Mohsen Forouzanfar; Saeede Soleimanian

doi:10.18502/ijaai.v22i4.13610

Nasrin Noshadi Department of Biology, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran
Ramin Yaghobi Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Afsoon Afshari Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Mohsen Forouzanfar Department of Biology, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran
Saeede Soleimanian Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

DOI: https://doi.org/10.18502/ijaai.v22i4.13610

Keywords: CD4 positive T lymphocytes; Cytotoxic; Human polyomavirus BK; Kidney transplantations; T-lymphocytes

Abstract

The reactivation of polyomavirus BK (BKPyV) contributes to increased morbidity and mortality rates of transplant patients, especially kidney transplant recipients (KTRs). CD4⁺ T cells are important immune cells active during BKPyV infection in KTRs. This research tried to examine the phenotype of CD4⁺ T cells in the stage of BKPyV activation in KTRs.

The recipients were separated into 2 groups of BKPyV-active and nonactive KTRs (10 patients in each group) and were compared with 10 healthy control subjects. The viral load was evaluated by Taq-man quantitative real-time PCR. The frequency of different CD4⁺ T cell subsets was determined by analyzing markers such as CD45RO, CCR7, CD27, CD107a, perforin, and granzyme B using flow cytometry. The gene expression levels of transcription factors, including TBX21, GATA3, STAT3, and STAT6, contributing to CD4⁺ T cell activation, were also assessed.

A significantly higher proportion in CCR7⁺CD27⁺CD45RO^-CD4⁺ T cell (naive Tcell) subsets was detected in BKPyV-active KTRs compared to nonactive ones. A significant increase was detected in the frequency of CD107a⁺, perforin⁺, and granzyme B⁺ CD4⁺ T cells in the BKPyV-active group compared to the nonactive group. In CD4⁺ T cells of KTRs, the mRNA expression of TBX21 and GATA3 was significantly increased in KTRs without BKPyV reactivation compared to BKPyV-active ones.

This investigation focused on the CD4⁺ T cell as an immunodominant T cell type with potential cytotoxicity. Based on these results, BKPyV may have a direct influence on the repertoire of CD4⁺ T cell subsets. Particularly, cytotoxic CD4⁺ T cells need further investigation to be considered as a therapeutic approach for BKPyV infection.