Persistent allopeptide reactivity and epitope spreading in chronic rejection of organ allografts

被引:242
作者
Ciubotariu, R
Liu, ZR
Colovai, AI
Ho, E
Itescu, S
Ravalli, S
Hardy, MA
Cortesini, R
Rose, EA
Suciu-Foca, N
机构
[1] Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA
[2] Columbia Univ, Coll Phys & Surg, Dept Surg, New York, NY 10032 USA
[3] Columbia Univ, Coll Phys & Surg, Dept Internal Med, New York, NY 10032 USA
[4] Univ Rome La Sapienza, Ist Clin Chirurg 2, Serv Trapianti Organo, Rome, Italy
关键词
indirect allorecognition; coronary artery vasculopathy; reactivity to HLA-DR allopeptides; intramolecular spreading; intermolecular spreading;
D O I
10.1172/JCI1117
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The role of the indirect allorecognition pathway in acute allograft rejection has been documented both in organ recipients and in experimental models. However, it is unknown whether self-restricted recognition of donor alloantigens also contributes to chronic allograft rejection. The aim of this study was to determine the relationship between allopeptide reactivity, epitope spreading, and chronic rejection. Using synthetic peptides corresponding to the hypervariable region of 32 HLA-DR alleles, we have followed the specificity of self-restricted T cell alloresponses to the donor in a population of 34 heart allograft recipients. T cells from sequential samples of blood collected from the patients up to 36 mo after transplantation were studied in limiting dilution analysis for allopeptide reactivity. The incidence of coronary artery vasculopathy (CAV) was significantly higher in patients who displayed persistent alloreactivity late after transplantation than in patients who showed no alloreactivity after the first 6 mo after transplantation. Both intra-and intermolecular spreading of epitopes was observed with an increased frequency in patients developing CAV in less than 2 yr, compared with patients without CAV; this suggests that diversification of the immune response against the graft contributes to chronic rejection. These data provide a strategy for identifying patients at risk of developing CAV and a rationale for therapeutic intervention aimed to prevent the progression of the rejection process.
引用
收藏
页码:398 / 405
页数:8
相关论文
共 53 条
  • [1] ALLEN MD, 1992, J HEART LUNG TRANSPL, V11, pS8
  • [2] BENICHOU G, 1994, J IMMUNOL, V153, P938
  • [3] BENICHOU G, 1996, INT REV IMMUNOL, V13, P245
  • [4] EVIDENCE FOR CLONAL ANERGY AS A MECHANISM RESPONSIBLE FOR THE MAINTENANCE OF TRANSPLANTATION TOLERANCE
    BRAUN, MY
    MCCORMACK, A
    WEBB, G
    BATCHELOR, JR
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 1993, 23 (07) : 1462 - 1468
  • [5] CASTEN LA, 1988, J IMMUNOL, V140, P404
  • [6] PEPTIDE-SPECIFIC PREVENTION OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS - NEONATAL TOLERANCE INDUCED TO THE DOMINANT T-CELL DETERMINANT OF MYELIN BASIC-PROTEIN
    CLAYTON, JP
    GAMMON, GM
    ANDO, DG
    KONO, DH
    HOOD, L
    SERCARZ, EE
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1989, 169 (05) : 1681 - 1691
  • [7] Colovai A I, 1996, Int Rev Immunol, V13, P161, DOI 10.3109/08830189609061745
  • [8] COSTANZONORDIN MR, 1992, J HEART LUNG TRANSPL, V11, pS90
  • [9] DEMETRIS AJ, 1989, TRANSPLANT P, V21, P3667
  • [10] IMMUNOLOGICALLY IGNORANT AUTOREACTIVE T-CELLS, EPITOPE SPREADING AND REPERTOIRE LIMITATION
    ELSON, CJ
    BARKER, RN
    THOMPSON, SJ
    WILLIAMS, NA
    [J]. IMMUNOLOGY TODAY, 1995, 16 (02): : 71 - 76