Phenotyping of TH9 Cells in Cytomegalovirus-reactivated Kidney Transplant Recipients

Human cytomegalovirus (HCMV) is a frequent complication in kidney transplant recipients (KTRs), often impacting immune regulation. TH9 cells, a subset of CD4+ T cells, are characterized by their secretion of interleukin-9 (IL-9). This study aimed to analyze the phenotypic profile of TH9 cells and their associated cytokine expression in KTRs, and to evaluate mRNA levels of IL-4 and transforming growth factor-β (TGF-β), key cytokines involved in TH9 differentiation. Ten HCMV+ and 10 HCMV- KTRs, along with 10 age- and sex-matched healthy controls, were enrolled. HCMV viral load was quantified using TaqMan real-time polymerase chain reaction. Flow cytometry was used to assess surface markers (CCR6+CCR4-IL-4Rα+CD4+) and intracellular IL-9 expression in TH9 cells. Gene expression levels of IL-4 and TGF-β were also assessed. Surface staining revealed a significantly higher frequency of CD4+CCR4- and CD4+CCR6+ T cells in HCMV- KTRs compared to HCMV+ patients. Conversely, the overall frequency of CD4+ TH9 cells was elevated in HCMV+ KTRs. Intracellular staining demonstrated a significant increase in CD4+IL-9+ and CD4+IL-4Rα+ T cells in the HCMV+ group. Additionally, mRNA expression levels of IL-4 and TGF-β were markedly higher in HCMV+ KTRs than in HCMV- counterparts. These findings suggest a potential role for TH9 cells and their signature cytokine IL-9 in the antiviral immune response in KTRs. While TH9 cells may contribute to HCMV-related immune modulation, further research is needed to fully elucidate their protective mechanisms against viral infections.   Keywords: ; ; ;