SPLIT TOLERANCE INDUCED BY ORTHOTOPIC LIVER-TRANSPLANTATION IN MICE

被引:64
作者
DAHMEN, U
QIAN, SG
RAO, AS
DEMETRIS, AJ
FU, FM
SUN, H
GAO, L
FUNG, JJ
STARZL, TE
机构
[1] UNIV PITTSBURGH,MED CTR,DEPT SURG,PITTSBURGH,PA 15213
[2] UNIV PITTSBURGH,MED CTR,DEPT PATHOL,PITTSBURGH,PA 15213
[3] UNIV PITTSBURGH,MED CTR,PITTSBURGH TRANSPLANT INST,PITTSBURGH,PA 15213
关键词
D O I
10.1097/00007890-199407150-00001
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Spontaneous orthotopic liver allograft acceptance associated with microchimerism in mice induces tolerance to subsequent skin or heart transplants from the donor but not third-party animals. Despite in vivo hyporesponsiveness, in vitro MLC and CTL assays showed continuing antidonor reactivity. Cells isolated from recipients' spleens and grafted livers, when tested in MLC and CTL assays, were antidonor reactive out to 3 months to the same degree as splenocytes obtained from either naive or presensitized (with skin or heart) mice. Nevertheless, passive transfer of splenocytes or liver lymphocytes from liver tolerant mice, but not naive or sensitized donor strain mice, were able to prolong skin graft survival significantly in naive irradiated recipients. By using a strain combination in which the donor but not the recipient expressed the stimulatory endogenous super-Ag (Mls(f)), it was possible to determine whether super-Ag-reactive T cells bearing V beta 5 and V beta 11 were deleted or anergic. Phenotypic analysis of cells isolated from recipients' spleens and grafted livers (up to 90 days after transplant), when compared with naive animals, showed no significant difference in V beta 5 and V beta 11 TCR expression. Additionally, when these isolated spleen cells were tested for antibody-mediated stimulation, both anti-V beta 5 and V beta 11 TCR mAb led to marked proliferation of cells obtained from naive and liver-transplanted recipients, but as expected, proliferation was very low in cells from naive donors. These results suggest that liver transplantation induces donor-specific tolerance in vivo, which may not be reflected in in vitro proliferative and cytotoxicity assays (split tolerance). Furthermore, this tolerance does not seem to be induced by clonal deletion or anergy of minor-lymphocyte-stimulating-antigen-reactive T cells in the recipients. recipients.
引用
收藏
页码:1 / 8
页数:8
相关论文
共 39 条
  • [11] STUDIES ON IMMUNOLOGICAL-TOLERANCE INDUCED IN MICE BY KIDNEY ALLOGRAFTS
    INOUE, K
    NIESEN, N
    ALBINI, B
    MILGROM, F
    [J]. INTERNATIONAL ARCHIVES OF ALLERGY AND APPLIED IMMUNOLOGY, 1991, 96 (04): : 358 - 361
  • [12] JONES LA, 1990, J EXP MED, V172, P1007
  • [13] LIVER-TRANSPLANTATION IN THE RAT - BIOCHEMICAL AND HISTOLOGICAL EVIDENCE OF COMPLETE TOLERANCE INDUCTION IN NON-REJECTOR STRAINS
    KAMADA, N
    DAVIES, HFS
    WIGHT, D
    CULANK, L
    ROSER, B
    [J]. TRANSPLANTATION, 1983, 35 (04) : 304 - 311
  • [14] CELLULAR BASIS OF TRANSPLANTATION TOLERANCE INDUCED BY LIVER GRAFTING IN THE RAT - EXTENT OF CLONAL DELETION AMONG THORACIC-DUCT LYMPHOCYTES, SPLEEN, AND LYMPH-NODE CELLS
    KAMADA, N
    TERAMOTO, K
    BAGUERIZO, A
    ISHIKAWA, M
    SUMIMOTO, R
    OHKOUCHI, Y
    [J]. TRANSPLANTATION, 1988, 46 (01) : 165 - 167
  • [15] FULLY ALLOGENEIC LIVER GRAFTING IN RATS INDUCES A STATE OF SYSTEMIC NONREACTIVITY TO DONOR TRANSPLANTATION ANTIGENS
    KAMADA, N
    BRONS, G
    DAVIES, HFS
    [J]. TRANSPLANTATION, 1980, 29 (05) : 429 - 431
  • [16] KAMADA N, 1985, TRANSPLANTATION, V39, P93
  • [17] KAMADA N, 1981, TRANSPLANT P, V13, P837
  • [18] T-CELL TOLERANCE BY CLONAL ELIMINATION IN THE THYMUS
    KAPPLER, JW
    ROEHM, N
    MARRACK, P
    [J]. CELL, 1987, 49 (02) : 273 - 280
  • [19] SELF-TOLERANCE ELIMINATES T-CELLS SPECIFIC FOR MLS-MODIFIED PRODUCTS OF THE MAJOR HISTOCOMPATIBILITY COMPLEX
    KAPPLER, JW
    STAERZ, U
    WHITE, J
    MARRACK, PC
    [J]. NATURE, 1988, 332 (6159) : 35 - 40
  • [20] T-CELL RECEPTOR V-BETA USE PREDICTS REACTIVITY AND TOLERANCE TO MLSA-ENCODED ANTIGENS
    MACDONALD, HR
    SCHNEIDER, R
    LEES, RK
    HOWE, RC
    ACHAORBEA, H
    FESTENSTEIN, H
    ZINKERNAGEL, RM
    HENGARTNER, H
    [J]. NATURE, 1988, 332 (6159) : 40 - 45