Abstract
The authors’ previous studies with 2 different adult patient populations demonstrated a correlation between indirect allorecognition of mismatched donor HLA Class I– and Class II–derived peptides and the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation. The aim of this study was to determine whether a parallel allorecognition of mismatched donor HLA Class I– and Class II–derived peptides occurs after lung transplantation and to determine its correlation with the development of BOS after lung transplantation in a group of pediatric patients.
Peripheral blood mononuclear cells from 7 BOS-positive and 6 BOS-negative pediatric lung transplant recipients (age, 11.5 ± 4.4 years) were cultured in the presence of synthetic peptides corresponding to the α-chain hypervariable regions of a mismatched donor HLA Class I molecule and the β-chain hypervariable region of a mismatched donor HLA-DR molecule. The frequencies of HLA Class I and Class II alloreactive T cells were determined using limiting dilution analysis.
A significant increase (
p = 0.025) in HLA Class I-alloreactive T cells was observed in BOS-positive patients (7.1 × 10
−5 ± 4.3 × 10
−5) compared with BOS-negative patients (2.1 × 10
−5 ± 1.8 × 10
−6). In addition, a significant increase (
p = 0.033) in HLA Class II-alloreactive T cells also was observed in BOS-positive patients (9.6 × 10
−5 ± 7.9 × 10
−5) compared with BOS-negative patients (1.3 × 10
−5 ± 2.1 × 10
−6).
This study indicates that a parallel CD4+ T-cell alloreactivity to both donor HLA Class I and Class II molecules may play a role in the pathogenesis of BOS both in adult and pediatric lung transplant recipients.