CD4+ /CD8+ T-cell ratio correlates with the graft fate in pig-to-non-human primate islet xenotransplantation

Abstract

Background: Xenogeneic islet transplantation using porcine pancreata has been a promising option for substituting human islet transplantation. Moreover, recent advances in pre-clinical results have put islet xenotransplantation closer to the possibility of clinical application. While preparing for the era of clinical xenotransplantation, developing non-invasive immune monitoring method which could predict the graft fate could benefit the patient. However, there are few reports showing predictive immune parameters associated with the fate of the graft in islet xenotransplantation.

Methods: The absolute number and ratio of T-cell subsets have been measured via flow cytometry from the peripheral blood of 16 rhesus monkeys before and after porcine islet xenotransplantation. The correlation between the graft survival and the absolute number or ratio of T cells was retrospectively analyzed.

Results: The ratio of CD4⁺ versus CD8⁺ T cells was significantly reduced due to CD8⁺ effector memory cells' increase. Correlation analyses revealed that CD4⁺ /CD8⁺ , CD4⁺ /CD8⁺ naïve, CD4⁺ naïve/CD8⁺ naïve, and CD4⁺ central memory/CD8⁺ naïve cell ratios negatively correlated with the duration of graft survival. Conversely, further analyses discovered strong, positive correlation of CD4⁺ /CD8⁺ cell ratios within the early graft-rejected monkeys (≤60 days).

Conclusions: This retrospective study demonstrated that CD4⁺ /CD8⁺ ratios correlated with graft survival, especially in recipients which rejected the graft in early post-transplantation periods. CD4⁺ /CD8⁺ ratios could be used as a surrogate marker to predict the graft fate in pig-to-NHP islet xenotransplantation.

Keywords: biomarker; immune monitoring; non-human primate; pancreatic islet; xenotransplantation.