Changes in T cell subsets in 12 patients enrolled in a tolerance induction protocol with combined kidney and hematopoietic cell transplantation (169.34)

Abstract

Abstract The goal of the study was to determine the changes in T cell subsets for up to 3 years in12 patients given HLA matched combined kidney and hematopoietic cell transplants using total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) as posttransplant conditioning. Eight of the 12 patients were successfully withdrawn from their immunosuppressive drugs. After the completion of the conditioning regimen the absolute number of CD3+T cells in the blood fell 10 by 100 fold in all patients as compared to the pretransplant levels. The greatest reduction was among the naïve CD4+ and CD8+ T cells. Among the CD4+ T cells the percentage of the naïve cells fell from about 40% pretransplant to about 2% at the nadir with a gradual increase thereafter to pretransplant levels during the end of the second year. In contrast, the percentage of Treg cells among CD4+ T cells increased about 3 fold after conditioning, and the ratio of Treg:naive CD4+ cells increased about 20 fold at that time. The change in the ratio approached the pretransplant value at about 6 months as the percentage of Treg cells declined and naive cells rose. During this period, there was upregulation of the expression of the PD-1 activation marker on both Treg and CD4+ Tcon cells, and transient increase in the ratio of NK T cells to naive T cells. Although T cell subsets returned to the pretransplant levels in the patients completely withdrawn from immunosuppressive drugs, no rejections were observed.