The effect of thymus transplantation on donor‐specific chimerism in the rat model of composite osseomusculocutaneous sternum, ribs, thymus, pectoralis muscles, and skin allotransplantation

The effect of thymus transplantation on donor‐specific chimerism in the rat model of composite osseomusculocutaneous sternum, ribs, thymus, pectoralis muscles, and skin allotransplantation:

Abstract

Introduction

Research on tolerance has proven that development of donor‐specific chimerism (DSC) may accompany tolerance induction in vascularized composite allotransplantation (VCA). In this study, we aimed to determine the effect of thymus transplantation on the induction of DSC in rat VCA model of osseomusculocutaneous sternum (OMCS) and osseomusculocutaneous sternum and thymus (OMCST) allotransplantation.

Materials and Methods

A total of 20 Lewis‐Brown Norway and Lewis rats, 5–6 weeks old, weighting between 120 and 150 g, were used in the study. OMCS (n = 5) and OMCST (n = 5) allografts were harvested from Lewis‐Brown Norway donors (RT1^l + n) based on the common carotid artery and external jugular vein, and a heterotopic transplantation was performed to the inguinal region of the Lewis (RT1^l) recipients under cyclosporine A monotherapy (16 mg/kg) protocol tapered to 2 mg/kg and maintained for the duration of the study. The peripheral blood chimerism levels (T‐cell, B‐cell, and monocyte/granulocyte/dendritic cell–MGDC populations) were evaluated at days 7, 14, 35, 63, 100, and 150 posttransplant by flow cytometry. At Day 150, thymus, spleen, and liver samples were assessed by polymerase chain reaction (PCR) in the presence of DSC.

Results

Total chimerism level increased in both OMCST and OMCS groups at all time points. At 150 days posttransplant, chimerism in OMCST group was significantly higher (12.91 ± 0.16%) than that in OMCS group (8.89 ± 0.53%%, p < .01), and PCR confirmed the presence of donor‐derived cells in the liver and spleen of all OMCST recipients and in one liver sample and two spleen samples in OMCS recipients without thymus transplant.

Conclusions

This study confirmed the direct effects of thymus transplantation on the induction and maintenance of DSC in T‐cell, B‐cell, and MGDC populations. These results confirm correlation between thymus transplantation and DSC induction.