间接同种异体识别机制：对经历急性同种异体移植排斥反应动物的MHC II类别肽特异性辅助性T细胞克隆的特征分析

Mechanisms of indirect allorecognition: characterization of MHC class II allopeptide-specific T helper cell clones from animals undergoing acute allograft rejection.

作者信息

Waaga A M, Chandraker A, Spadafora-Ferreira M, Iyengar A R, Khoury S J, Carpenter C B, Sayegh M H

机构信息

Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

出版信息

Transplantation. 1998 Apr 15;65(7):876-83. doi: 10.1097/00007890-199804150-00004.

DOI:10.1097/00007890-199804150-00004

PMID:9565089

Abstract

BACKGROUND

Recent evidence indicates that T cells primed via the indirect pathway of allorecognition play an important role in allograft rejection, although the effector mechanisms remain unknown. The purpose of this study was to characterize and study the in vivo function of self-restricted MHC allopeptide-specific T-cell clones generated from animals undergoing allograft rejection.

METHODS AND RESULTS

We generated self-restricted class II MHC allopeptide-specific T-cell clones from the spleen and kidney of Lewis (LEW; RT1l) rats undergoing acute rejection of MHC-incompatible Wistar Furth (WF; RT1u) renal allografts. RT1.Du/beta20-44 peptide-specific CD4+ T helper 1 clones from the spleen and kidney of rejecting animals expressed a restricted T cell receptor (TCR) Vbeta repertoire: Vbeta4, 8.2, or 9. In comparison, clones generated from RT1.Dubeta20-44 immunized LEW rats all expressed TCR Vbeta9. The amino acid sequence of RT1.Dl (LEW) and RT1.Du (WF) residues 20-44 differ only at positions 30 and 38. T-cell clones expressing TCR Vbeta9 preferentially proliferated to the peptide fragment RT1.Dubeta20-33. T-cell clones expressing TCR Vbeta4 proliferated weakly to peptide fragments RT1.Dubeta20-33 and 31-44, whereas those expressing TCR Vbeta8.2 proliferated preferentially to the peptide fragment 31-44. Adoptive transfer of T-cell clones expressing TCR Vbeta9 or Vbeta8.2, but not Vbeta4, to naive LEW animals elicited significant delayed-type hypersensitivity responses after challenge with the RT1.Dubeta20-44 peptide or allogeneic WF (RT1u) splenocytes.

CONCLUSION

This is the first report on the cellular, molecular, and functional characterization of self-restricted MHC allopeptide-specific T-cell clones from animals undergoing acute rejection. Our data provide support for a biologically significant role of indirect allorecognition in allograft rejection.

摘要

背景

近期证据表明，经由同种异体识别间接途径致敏的T细胞在同种异体移植排斥反应中发挥重要作用，尽管其效应机制尚不清楚。本研究的目的是对同种异体移植排斥反应动物体内产生的自身限制性MHC同种异体肽特异性T细胞克隆进行表征并研究其体内功能。

方法与结果

我们从正在经历MHC不相容的Wistar Furth（WF；RT1u）肾移植急性排斥反应的Lewis（LEW；RT1l）大鼠的脾脏和肾脏中产生了自身限制性II类MHC同种异体肽特异性T细胞克隆。来自排斥反应动物脾脏和肾脏的RT1.Du/beta20 - 44肽特异性CD4 + T辅助1克隆表达受限的T细胞受体（TCR）Vbeta谱系：Vbeta4、8.2或9。相比之下，从经RT1.Dubeta20 - 44免疫的LEW大鼠中产生的克隆均表达TCR Vbeta9。RT1.Dl（LEW）和RT1.Du（WF）第20 - 44位残基的氨基酸序列仅在第30和38位不同。表达TCR Vbeta9的T细胞克隆优先增殖至肽片段RT1.Dubeta20 - 33。表达TCR Vbeta4的T细胞克隆对肽片段RT1.Dubeta20 - 33和31 - 44增殖较弱，而表达TCR Vbeta8.2的克隆优先增殖至肽片段31 - 44。将表达TCR Vbeta9或Vbeta8.2而非Vbeta4的T细胞克隆过继转移至未致敏的LEW动物，在用RT1.Dubeta20 - 44肽或同种异体WF（RT1u）脾细胞攻击后引发显著的迟发型超敏反应。