Donor-Derived Lymphocyte Chimerism is Associated with Protection from Chronic Lung Allograft Dysfunction

PurposeDonor-derived lymphocyte chimerism is proposed to have a protective effect on allograft health. This study aimed to identify the association between the persistence of donor-derived lymphocytes in the blood and bronchoalveolar lavage (BAL) of lung transplant (LTx) recipients and the development of chronic lung allograft dysfunction (CLAD).MethodsFlow cytometric analyses were performed on blood and BAL samples from LTx recipients from 2-78 weeks post-LTx utilizing: 1) a panel of antibodies to characterize lymphocyte identity, proliferation, and tissue residency (CD69 and CD103);2) HLA antibodies to distinguish donor and recipient cells. These findings were then correlated to the development of CLAD by 3 years post-LTx.ResultsThe persistence of BAL donor-derived lymphocytes, which contained T cells and NK cells, was associated with CLAD protection (Figure 1). Few donor lymphocytes were detected by flow cytometry in the blood beyond 6 weeks. Donor BAL lymphocytes were largely CD69+ and were initially dominant in the CD103+ compartment. Donor-derived lymphocytes underwent proliferation very infrequently compared to the recipient-derived cells. Recipient cells acquired CD103 over time, eventually replacing CD103+ donor-derived cells in this compartment.ConclusionThe persistence of donor-derived lymphocytes in the lung compartment can be used to predict future allograft health. Further work is required to determine if this represents a measure of graft tolerance.L.C. and S.S. contributed equally to this work. Donor-derived lymphocyte chimerism is proposed to have a protective effect on allograft health. This study aimed to identify the association between the persistence of donor-derived lymphocytes in the blood and bronchoalveolar lavage (BAL) of lung transplant (LTx) recipients and the development of chronic lung allograft dysfunction (CLAD). Flow cytometric analyses were performed on blood and BAL samples from LTx recipients from 2-78 weeks post-LTx utilizing: 1) a panel of antibodies to characterize lymphocyte identity, proliferation, and tissue residency (CD69 and CD103);2) HLA antibodies to distinguish donor and recipient cells. These findings were then correlated to the development of CLAD by 3 years post-LTx. The persistence of BAL donor-derived lymphocytes, which contained T cells and NK cells, was associated with CLAD protection (Figure 1). Few donor lymphocytes were detected by flow cytometry in the blood beyond 6 weeks. Donor BAL lymphocytes were largely CD69+ and were initially dominant in the CD103+ compartment. Donor-derived lymphocytes underwent proliferation very infrequently compared to the recipient-derived cells. Recipient cells acquired CD103 over time, eventually replacing CD103+ donor-derived cells in this compartment. The persistence of donor-derived lymphocytes in the lung compartment can be used to predict future allograft health. Further work is required to determine if this represents a measure of graft tolerance.