TY - JOUR
T1 - Concomitant allorecognition of mismatched donor HLA class I- and class II- derived peptides in pediatric lung transplant recipients with bronchiolitis obliterans syndrome
AU - Lu, Kim C.
AU - Jaramillo, Andrés
AU - Mendeloff, Eric N.
AU - Huddleston, Charles B.
AU - Sweet, Stuart C.
AU - Patterson, G. Alexander
AU - Mohanakumar, T.
PY - 2003/1/1
Y1 - 2003/1/1
N2 - Background: 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. Methods: 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. Results: 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). Conclusions: 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.
AB - Background: 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. Methods: 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. Results: 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). Conclusions: 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.
UR - http://www.scopus.com/inward/record.url?scp=0037229946&partnerID=8YFLogxK
U2 - 10.1016/S1053-2498(02)00478-3
DO - 10.1016/S1053-2498(02)00478-3
M3 - Article
C2 - 12531411
AN - SCOPUS:0037229946
SN - 1053-2498
VL - 22
SP - 35
EP - 43
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
IS - 1
ER -