Concomitant allorecognition of mismatched donor HLA Class I- and class II-derived peptides in pediatric lung transplant recipients with bronchiolitis oblitetans syndrome

被引:24
作者
Lu, KC
Jaramillo, A
Mendeloff, EN
Huddleston, CB
Sweet, SC
Patterson, GA
Mohanakumar, T
机构
[1] Washington Univ, Dept Surg, Sch Med, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
关键词
D O I
10.1016/S1053-2498(02)00478-3
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 ut-chain hypervariable regions of a mismatched donor HLA Class I molecule and the beta-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 X 10(-5) +/- 4.3 X 10(-5)) compared with BOS-negative patients (2.1 X 10(-5) +/- 1.8 X 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 X 10(-5) +/- 7.9 X 10(-5)) compared with BOS-negative patients (1.3 X 10(-5) +/- 2.1 X 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.
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页码:35 / 43
页数:9
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