Abstract Body: Previous work in our laboratory demonstrated that CD4+ T cells amplify salt-sensitive hypertension and renal damage in Dahl Salt-Sensitive (SS) rats while CD8+ T cells do not contribute to the Dahl SS disease phenotype. The present study aimed to translate these findings; we hypothesized that CD4+ T cell presence correlates with kidney disease in humans. We utilized immunohistochemistry (IHC), flow cytometry, and CyTOF (Cytometry by Time of Flight) to study kidneys from 12 donors (6 male/6 female; 45-70 years of age; 5 African American/6 Caucasian/ 1 unknown) rejected for transplantation and obtained through the organ procurement organization, LifeLink® of Georgia. The IHC analysis indicated a consistent distribution of CD3+ and CD4+ staining throughout the human kidneys with the most prominent clustering observed within the corticomedullary boundary, a pattern also observed in Dahl SS kidneys. Furthermore, consistent with increased CD4+ T cells in the kidney of hypertensive Dahl SS rats, flow cytometry demonstrated a positive association between renal damage (pathologist-defined percentage of sclerosed glomeruli) and the number of CD3+ T cells (Spearman r: 0.79, p<0.01) and CD4+ T helper cells (Spearman r: 0.67, p<0.05) per gram of human kidney tissue. Notably, the majority of donors with the greatest number of T cells in the kidney and the highest percentage of glomerulosclerosis were subjects with a documented history of hypertension. Finally, preliminary CyTOF analysis demonstrated an average of 28.2±10% CD45+CD3+ T cells in a subset of human kidneys (n=3) in which 29.4±11% were comprised of CD4+ cells including 20.5±12% CD4+CD127+ cells (IL-17RA+) and 4.5±1% CD4+CD25+ cells (regulatory T cells). The CD4+ T cells were also further characterized as 16.9±12% central memory T cells (CCR7+CD45RO+CD45RA-), 36.1±5% effector memory T cells (CCR7-CD45RO+CD45RA-), 8±2% naïve T cells (CCR7+CD45RO-CD45RA+), and 34.5±14% effector T cells (CCR7+CD45RO-CD45RA+). These data demonstrate an association between CD4+ T cells and kidney injury in humans, consistent with observations in the Dahl SS preclinical rat model, highlighting the potential for T cell-based immunotherapies for the treatment of hypertension-associated kidney disease.