Lu Kim C, Jaramillo Andrés, Mendeloff Eric N, Huddleston Charles B, Sweet Stuart C, Patterson G Alexander, Mohanakumar T
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Heart Lung Transplant. 2003 Jan;22(1):35-43. doi: 10.1016/s1053-2498(02)00478-3.
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 alpha-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.
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)).
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.
作者之前对两组不同成年患者群体的研究表明，不匹配供体的 HLA Ⅰ类和Ⅱ类衍生肽的间接同种异体识别与肺移植后闭塞性细支气管炎综合征（BOS）的发生之间存在相关性。本研究的目的是确定在一组儿科患者中，肺移植后是否会出现对不匹配供体 HLA Ⅰ类和Ⅱ类衍生肽的平行同种异体识别，并确定其与肺移植后 BOS 发生的相关性。
将 7 例 BOS 阳性和 6 例 BOS 阴性儿科肺移植受者（年龄 11.5±4.4 岁）的外周血单个核细胞，在对应于不匹配供体 HLA Ⅰ类分子α链高变区和不匹配供体 HLA-DR 分子β链高变区的合成肽存在的情况下进行培养。使用有限稀释分析法确定 HLA Ⅰ类和Ⅱ类同种异体反应性 T 细胞的频率。
与 BOS 阴性患者（2.1×10⁻⁵±1.8×10⁻⁶）相比，BOS阳性患者（7.1×10⁻⁵±4.3×10⁻⁵）中观察到 HLA Ⅰ类同种异体反应性 T 细胞显著增加（p = 0.025）。此外，与 BOS 阴性患者（1.3×10⁻⁵±2.1×10⁻⁶）相比，BOS 阳性患者（9.6×10⁻⁵±7.9×10⁻⁵）中也观察到 HLA Ⅱ类同种异体反应性 T 细胞显著增加（p = 0.033）。
本研究表明，对供体 HLA Ⅰ类和Ⅱ类分子的平行 CD4⁺T 细胞同种异体反应性可能在成人和儿科肺移植受者 BOS 的发病机制中起作用。
Zotero 插件