Evidence for clonal deletion and clonal anergy after intrathymic antigen injection in a transplantation model

被引:16
作者
Gillanders, WE
Arima, T
Tu, F
Hansen, TH
Flye, MW
机构
[1] WASHINGTON UNIV,SCH MED,DEPT SURG,ST LOUIS,MO 63110
[2] WASHINGTON UNIV,SCH MED,DEPT GENET,ST LOUIS,MO 63110
关键词
D O I
10.1097/00007890-199710270-00014
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Intrathymic (IT) antigen injection has been shown to induce antigen-specific systemic tolerance in the rodent. To delineate the mechanisms responsible for the induction of tolerance, we used the 2C line of T cell receptor transgenic mice. The majority of T cells in 2C mice express an antigen receptor specific for the major histocompatibility complex class I alloantigen L-d and can be identified with the clonotypic monoclonal antibody 1B2. IT injection of lymphoid cells expressing L-d was found to induce a significant prolongation in BALB/c skin allograft survival. The allograft prolongation was associated with a marked reduction in the number of developing 1B2(+) thymocytes (clonal deletion), which occurred primarily at the CD4(+)CD8(+) stage of thymocyte development, as well as a reduction in the number of mature CD8(+)1B2(+) 2C T cells in peripheral lymphoid tissue. In addition, CD8(+)1B2(+) 2C T cells that survive deletion have decreased CD8 expression levels and a significantly reduced in vitro proliferative response to specific alloantigen (clonal anergy). Exogenous recombinant interleukin 2 restores the capacity of 2C T cells to respond in vitro to alloantigen. Experiments involving separation of cells by fluorescence-activated cell sorter indicate that there is a precise correlation between the reduction in CD8 expression and anergy induction. Collectively, these data indicate that IT antigen injection can induce antigen-specific systemic tolerance by both clonal deletion and clonal anergy.
引用
收藏
页码:1159 / 1166
页数:8
相关论文
共 39 条
[1]   NEGATIVE AND POSITIVE SELECTION OF ANTIGEN-SPECIFIC CYTOTOXIC LYMPHOCYTES-T AFFECTED BY THE ALPHA-3 DOMAIN OF MHC-I MOLECULES [J].
ALDRICH, CJ ;
HAMMER, RE ;
JONESYOUNGBLOOD, S ;
KOSZINOWSKI, U ;
HOOD, L ;
STROYNOWSKI, I ;
FORMAN, J .
NATURE, 1991, 352 (6337) :718-721
[2]   CORRELATION BETWEEN CD8 DEPENDENCY AND DETERMINANT DENSITY USING PEPTIDE-INDUCED, LD-RESTRICTED CYTOTOXIC LYMPHOCYTES-T [J].
ALEXANDER, MA ;
DAMICO, CA ;
WIETIES, KM ;
HANSEN, TH ;
CONNOLLY, JM .
JOURNAL OF EXPERIMENTAL MEDICINE, 1991, 173 (04) :849-858
[3]   A DIFFERENTIAL-AVIDITY MODEL FOR T-CELL SELECTION [J].
ASHTONRICKARDT, PG ;
TONEGAWA, S .
IMMUNOLOGY TODAY, 1994, 15 (08) :362-366
[4]   EVIDENCE FOR A DIFFERENTIAL AVIDITY MODEL OF T-CELL SELECTION IN THE THYMUS [J].
ASHTONRICKARDT, PG ;
BANDEIRA, A ;
DELANEY, JR ;
VANKAER, L ;
PIRCHER, HP ;
ZINKERNAGEL, RM ;
TONEGAWA, S .
CELL, 1994, 76 (04) :651-663
[5]  
BILLINGHAM RE, 1951, J EXP BIOL, V28, P385
[6]   RESTING AND ACTIVATED T-CELLS DISPLAY DIFFERENT REQUIREMENTS FOR CD8 MOLECULES [J].
CAI, ZL ;
SPRENT, J .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 179 (06) :2005-2015
[7]  
CAMPOS L, 1993, TRANSPLANTATION, V54, P1090
[8]   STRONG T-CELL TOLERANCE IN PARENT-]F1 BONE-MARROW CHIMERAS PREPARED WITH SUPRALETHAL IRRADIATION - EVIDENCE FOR CLONAL DELETION AND ANERGY [J].
GAO, EK ;
LO, D ;
SPRENT, J .
JOURNAL OF EXPERIMENTAL MEDICINE, 1990, 171 (04) :1101-1121
[9]  
GOSS JA, 1994, J IMMUNOL, V153, P3890
[10]   INTRATHYMIC INJECTION OF DONOR ALLOANTIGENS INDUCES SPECIFIC TOLERANCE TO CARDIAC ALLOGRAFTS [J].
GOSS, JA ;
NAKAFUSA, Y ;
YU, S ;
FLYE, MW .
TRANSPLANTATION, 1993, 56 (01) :166-173