CD28 Expression on T Cells as a Biomarker for Allograft Rejection in Renal Transplant Recipients

To evaluate the differences in pre-transplant CD28 expression on T cell subsets between rejectors and non-rejectors of renal transplant, and their potential role in post-transplant outcomes.

A descriptive cross-sectional study. Place and Duration of the Study: Department of Immunology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from August 2023 to March 2025.

Sixty live-related renal transplant recipients were enrolled after ethical approval. Flow cytometry was used to analyse CD28 expression on T cell subsets before transplantation. Patients were stratified into rejectors and non-rejectors based on biopsy findings between 6 and 18 months post-transplantation. Independent samples t-test and Mann-Whitney U test were used to compare the means of different cell populations between the two groups. A p <0.05 was considered statistically significant.

While the frequency and absolute counts of CD3+CD28-, CD4+CD28-, and CD8+CD28- T cells were lower in rejectors as compared to non-rejectors, these differences were statistically insignificant. A significantly higher percentage of CD8+CD28+ T cells was observed in rejectors (19.7% vs. 14.2%, p <0.001), with logistic regression revealing a 25% increased rejection risk per 1% rise in CD8+ CD28+ cells (OR: 1.25, 95% CI: 1.037-1.507). These findings support the hypothesis that CD28- T cells, which often expand in ESRD due to immune senescence, may confer protection against allograft rejection. In contrast, elevated CD28+ T cells may reflect heightened alloimmune potential leading to graft rejection.

Pre-transplant profiling of CD28+ and CD28- T cell subsets appears to hold promise as a tool for immunological risk assessment in kidney transplantation. However, further large-scale studies are required to establish its reliability and cut-off values for use in clinical practice.

Graft rejection, Kidney transplantation, Risk assessment, Transplantation immunology.