Lack of systemic cellular immune response in children and young adults receiving decellularized allografts

Objectives: Longevity of homografts is determined by activation of the recipients' immune system as a result to allogenic antigen exposition. Decellularized homografts (DH), which have shown promising early results in pulmonary valve replacement in children and young adults, could potentially avoid significant activation of the immune system, as more than 99% of donor DNA is removed during the decellularization process. So far, only the humoral immune response against decellularized allografts has been studied. Detailed information on the cellular immune response is still missing. The aim of this study was to evaluate, whether implantation of a fresh decellularized human allograft induces a cellular immune response.

Methods: Peripheral blood samples were obtained from patients undergoing pulmonary valve replacement with DH before, after, and up to 3 years after the operation. Absolute counts and percentages of mature T- (CD3), B- (CD19) and NK- (CD56) cells, as well as T helper- (CD4) and cytotoxic T-cell (CD8) subsets, were determined by FACS-analysis.

Results: Between May 2009 and July 2012, 153 blood samples from 61 patients (mean age 17.8 years ± 13.4 years, range 1 month – 50yrs.) with DH were analyzed. Hemodynamic performance of DH was excellent. No valve related deaths or conduit explantations were observed. Short term follow-up revealed a mild decrease in cell count of most subtypes with reconstitution after 3 months, while further follow-up did not show any significant deviation of numbers of cell subsets. Figure 1 exemplarily shows the time course of mature T-cells (CD3).

Fig. 1: CD3-positive T-cells

Conclusion: The lack of immune response in patients receiving DH supports the concept of decellularization as the basis for autologeous regeneration.