Indirect Allorecognition of Mismatched Donor HLA Class II Peptides in Lung Transplant Recipients with Bronchiolitis Obliterans Syndrome

Abstract

A correlation between indirect allorecognition of mismatched donor HLA class I peptides and development of bronchiolitis obliterans syndrome (BOS) after lung transplantation has been previously observed. The aim of this study was to determine whether there was a correlation between indirect allorecognition of mismatched donor HLA class II peptides and development of BOS after lung transplantation. Peripheral blood mononuclear cells from nine BOSπ and nine BOSlung transplant recipients were cultured with synthetic peptides corresponding to the b-chain hypervariable region of a mismatched donor HLA-DR molecule. Then, proliferative alloreactivity as well as frequency of alloreactive T cells were determined. In addition, the immunodominant epitopes from the donor HLA-DR molecules were identified in selected patients. T cells from BOSπ patients showed a dose-dependent proliferative alloreactivity against donor HLA-DR peptides that was significantly higher than that observed in BOS-patients (pΩ0.001). Similarly, the frequency of HLA-DR alloreactive T cells was significantly higher in BOSπ patients than in BOS-patients (pΩ0.001). This T-cell alloreactivity was directed against a single immunodominant HLA-DR peptide. These results suggest that indirect alloreactivity to donor HLA class II molecules may play a role in the pathogenesis of BOS after lung transplantation.

Soluble CD30 levels as a diagnostic marker for bronchiolitis obliterans syndrome following human lung transplantation

“…Although the exact role of CD30 in the pathogenesis of BOS is unknown, alloimmune response is considered as a major contributor in the immuno-pathogenesis of BOS (5,16,17). We have shown that BOS+ patients develop early post-transplant inflammation which may activate allo-as well as auto-immunity (18).…”

“…BOS is histologically characterized by cellular infiltration, fibrosis, collagen deposition and occlusion of small airways in the allograft (4). The role of T cell immunity in the pathogenesis of chronic lung allograft rejection both in clinical lung transplantation and in animal models of obliterative airway diseases has been well established (5,6). Therefore, it is reasonable to predict that sCD30 which is a marker for T cell activation may increase during rejection of the allograft.…”

Antigen Location Contributes to the Pathological Features of a Transplanted Heart Graft

“…[51][52][53][54] Nonetheless, a gap exists between our understanding of how T cells are activated through the indirect pathway and how such activated T cells predominantly induce chronic pathology. The results presented in this report provide a potential explanation to bridge this gap.…”

How Can We Measure Immunologic Tolerance in Humans?

“…In this regard, one important point is that over time after organ transplantation, T cells may recognize different epitopes of donor antigens in the same individuals, a process called epitope spreading. This phenomenon has been described in renal (39), cardiac (40), and lung transplant recipients (41). This process has been implicated as a mechanism for continual recruitment of naïve alloreactive T cells, which may contribute toward acute and chronic rejection.…”