Unsupervised Immune Profiling Identifies Distinct Post-Transplant T-Cell Clusters Associated with Kidney Allograft...

Area of Science:

• Immunology
• Transplantation Biology
• Renal Medicine

Background:

• Immune heterogeneity post-kidney transplant can impact allograft success.
• The clinical significance of circulating T-cell phenotypes is not fully understood.

Purpose of the Study:

• To identify T-cell clusters based on 12-month post-transplant data.
• To investigate the relationship between these T-cell clusters and kidney graft function patterns within the first year.

Main Methods:

• Flow cytometry analyzed T-cell subpopulations in 112 kidney transplant recipients at 12 months.
• Unsupervised hierarchical clustering and principal component analysis were used for T-cell data.
• Longitudinal graft function (eGFR, creatinine) was assessed using generalized estimating equation models.

Main Results:

• Three distinct T-cell clusters emerged: CD8-skewed cytotoxic/senescent, innate-like cytotoxic, and CD4-dominant.
• Older age and cytomegalovirus seropositivity were linked to the CD8-skewed cluster.
• Differences in serum creatinine and graft function trajectories were observed across clusters, though some associations were attenuated.

Conclusions:

• Unsupervised clustering identified specific T-cell profiles associated with early kidney graft function.
• These findings suggest T-cell phenotypes may influence early transplant outcomes.
• Further longitudinal and external validation is required.