SUPERANTIGEN-REACTIVE T-CELLS THAT DISPLAY AN ANERGIC PHENOTYPE IN-VITRO APPEAR FUNCTIONAL IN-VIVO

被引:26
作者
HEEG, K
GAUS, H
GRIESE, D
BENDIGS, S
MIETHKE, T
WAGNER, H
机构
[1] Institute of Medical Microbiology and Hygiene, Technical University of Munich, D-81675 Munich
关键词
ANERGY; CD4(+) T CELLS; IL-2; REVERSION OF ANERGY; STAPHYLOCOCCAL ENTEROTOXIN B; SUPERANTIGEN; T CELL-MEDIATED SHOCK; TUMOR NECROSIS FACTOR;
D O I
10.1093/intimm/7.1.105
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Clonal deletion and/or inactivation establishes tolerance to self antigens. Endogenous and exogenous (bacterial) superantigens, like the staphylococcal enterotoxins, induce ligand-specific clonal anergy in vivo and thus are believed to mirror aspects of post-thymic tolerance mechanisms in mature peripheral T cells. Here we analyzed the level of anergy of ligand-responsive V(beta)8(+) T cells from staphylococcal enterotoxin B (SEB)-primed mice in vivo and in vitro. Upon in vitro restimulation with SEB, CD4(+)V(beta)8(+) and CD8(+)V(beta)8(+) T cells failed to produce IL-2. However, functional IL-2 receptors were triggered, since supplementation with IL-2 induced clonal growth in virtually all CD4(+)V(beta)8(+) and CD8(+)V(beta)8(+) T cells as determined by limiting dilution analyses. Thus in vitro unresponsiveness of lymphocytes from SEE-primed mice reflects the inability of SEB-reactive V(beta)8(+) T cells to produce IL-2. Surprisingly anergy as defined in vitro was at variance with that in vivo. Following further challenge with SEB, systemic and acute lymphokine production (including IL-2 and tumor necrosis factor) occurred with almost identical peak values and kinetics to primary in vivo responses, and D-galactosamine-sensitized mice succumbed to lethal shock. Polymerase chain reaction analyses revealed that CD4(+)V(beta)8(+) expressed IL-2-specific mRNA in vivo upon restimulation with SEB. While lymphokine production and expression of the IL-2 receptor was similar to the response to in vivo primary stimulation, only CD8(+) V(beta)8(+) T cells expanded clonally upon reintroduction of SEB in vivo, Hence primed V(beta)8(+) T cells challenged with SEB display in vitro anergy yet in vivo responsiveness, at least in part. We conclude that the state of anergy is reversible, dependent upon the quality of activation signals provided in in vivo rather than in in vitro culture conditions.
引用
收藏
页码:105 / 114
页数:10
相关论文
共 60 条
  • [1] CLONAL DELETION OF THYMIC MATURE T-CELLS INDUCED BY STAPHYLOCOCCAL ENTEROTOXIN-B IN MURINE FETAL THYMUS ORGAN-CULTURE
    AIBA, Y
    MAZDA, O
    MATSUZAKI, Y
    NAKAUCHI, H
    MURAMATSU, S
    KATSURA, Y
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 1993, 23 (04) : 815 - 819
  • [2] PROLIFERATIVE T-CELL ANERGY TO MLS-1A DOES NOT CORRELATE WITH INVIVO TOLERANCE
    BANDEIRA, A
    MENGEL, J
    BURLENDEFRANOUX, O
    COUTINHO, A
    [J]. INTERNATIONAL IMMUNOLOGY, 1991, 3 (09) : 923 - 931
  • [3] CLONAL ANERGY TO STAPHYLOCOCCAL ENTEROTOXIN-B IN-VIVO - SELECTIVE EFFECTS ON T-CELL SUBSETS AND LYMPHOKINES
    BASCHIERI, S
    LEES, RK
    LUSSOW, AR
    MACDONALD, HR
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 1993, 23 (10) : 2661 - 2666
  • [4] TRANSGENIC MICE WITH I-A ON ISLET CELLS ARE NORMOGLYCEMIC BUT IMMUNOLOGICALLY INTOLERANT
    BOHME, J
    HASKINS, K
    STECHA, P
    VANEWIJK, W
    LEMEUR, M
    GERLINGER, P
    BENOIST, C
    MATHIS, D
    [J]. SCIENCE, 1989, 244 (4909) : 1179 - 1183
  • [5] T-CELL TOLERANCE BY CLONAL ANERGY IN TRANSGENIC MICE WITH NONLYMPHOID EXPRESSION OF MHC CLASS-II I-E
    BURKLY, LC
    LO, D
    KANAGAWA, O
    BRINSTER, RL
    FLAVELL, RA
    [J]. NATURE, 1989, 342 (6249) : 564 - 566
  • [6] PERIPHERAL TOLERANCE THROUGH CLONAL DELETION OF MATURE CD4- CD8+ T-CELLS
    CARLOW, DA
    TEH, SJ
    VANOERS, NSC
    MILLER, RG
    TEH, HS
    [J]. INTERNATIONAL IMMUNOLOGY, 1992, 4 (05) : 599 - 610
  • [7] DANNECKER G, 1991, J IMMUNOL, V146, P2083
  • [8] GODING JW, 1986, MONOCLONAL ANTIBODIE, P255
  • [9] EXPANSION AND CLONAL DELETION OF PERIPHERAL T-CELLS INDUCED BY BACTERIAL SUPERANTIGEN IS INDEPENDENT OF THE INTERLEUKIN-2 PATHWAY
    GONZALO, JA
    DEALBORAN, IM
    ALESMARTINEZ, JE
    MARTINEZA, C
    KROEMER, G
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 1992, 22 (04) : 1007 - 1011
  • [10] INDUCTION OF PERIPHERAL TOLERANCE TO CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) ALLOANTIGENS IN ADULT MICE - TRANSFUSED CLASS-I MHC-INCOMPATIBLE SPLENOCYTES VETO CLONAL RESPONSES OF ANTIGEN-REACTIVE LYT-2+ T-CELLS
    HEEG, K
    WAGNER, H
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1990, 172 (03) : 719 - 728