Staphylococcal enterotoxin B stimulates expansion of autoreactive T cells that induce apoptosis in intestinal epithelial cells: Regulation of autoreactive responses by IL-10

被引:25
作者
Ito, K
Takaishi, H
Jin, Y
Song, F
Denning, TL
Ernst, PB
机构
[1] Univ Texas, Dept Pediat, Med Branch, Galveston, TX 77555 USA
[2] Univ Texas, Dept Microbiol & Immunol, Med Branch, Galveston, TX 77555 USA
[3] Univ Texas, Sealy Ctr Mol Sci, Med Branch, Galveston, TX 77555 USA
关键词
D O I
10.4049/jimmunol.164.6.2994
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
T cell responses to self Ags and normal microbial flora are carefully regulated to prevent autoreactivity, Because IL-10-deficient mice develop colitis, and this response is triggered by luminal flora, we investigated whether IL-10 regulates the ability of microbial Ags to induce autoreactive T cells that could contribute to intestinal inflammation, T cells from mild-type mice were primed with staphylococcal enterotoxin B (SEB) in vitro, which induced an autoreactive proliferative response to syngeneic feeder cells, The cells mere predominately CD3(+) and CD4(+), T cells from IL-10-deficient mice were constitutively autoreactive, and SEE priming enhanced this further, The autoreactive, proliferative response of T cells from wild-type mice was Suppressed by IL-10 in the primary or secondary culture, and this effect was inhibited by neutralizing Abs to the IL-10R. To confirm that an autoreactive repertoire was expanded after SEE priming, we used CBA/J mice (Mls-1(a)) in which autoreactive T cells recognizing the endogenous viral superantigen are depleted (V beta 6, 7, 8.1 TCR-bearing cells). However, SEE rescued these autoreactive T cell repertoires, Adding anti-MHC class II. Ab blocked the autoreactive response. SEE-primed splenic or colonic T cells also induced apoptosis in syngeneic intestinal epithelial cells that was blocked significantly by IL-10. Thus, microbial Ags have the potential to abrogate self tolerance by stimulating autoreactive T cells that become cytolytic to target cells, IL-10 plays a protective role in maintaining self tolerance after microbial stimulation by preventing the activation of T cells that contribute to epithelial cell damage.
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页码:2994 / 3001
页数:8
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共 56 条
  • [11] Dianda L, 1997, AM J PATHOL, V150, P91
  • [12] DING L, 1993, J IMMUNOL, V151, P1224
  • [13] Duchmann R, 1995, CLIN EXP IMMUNOL, V102, P448
  • [14] Tolerance towards resident intestinal flora in mice is abrogated in experimental colitis and restored by treatment with interleukin-10 or antibodies to interleukin-12
    Duchmann, R
    Schmitt, E
    Knolle, P
    zumBuschenfelde, KHM
    Neurath, M
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 1996, 26 (04) : 934 - 938
  • [15] ERNST PB, 1987, CELL SEPARATION METH, V5, P141
  • [16] FIORENTINO DF, 1991, J IMMUNOL, V147, P3815
  • [17] FIORENTINO DF, 1991, J IMMUNOL, V146, P3444
  • [18] A CD4(+) T-cell subset inhibits antigen-specific T-cell responses and prevents colitis
    Groux, H
    OGarra, A
    Bigler, M
    Rouleau, M
    Antonenko, S
    deVries, JE
    Roncarolo, MG
    [J]. NATURE, 1997, 389 (6652) : 737 - 742
  • [19] Interleukin-10 induces a long-term antigen-specific anergic state in human CD4(+) T cells
    Groux, H
    Bigler, M
    deVries, JE
    Roncarolo, MG
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (01) : 19 - 29
  • [20] Altered immune responses in interleukin 10 transgenic mice
    Hagenbaugh, A
    Sharma, S
    Dubinett, SM
    Wei, SHY
    Aranda, R
    Cheroutre, H
    Fowell, DJ
    Binder, S
    Tsao, B
    Locksley, RM
    Moore, KW
    Kronenberg, M
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 185 (12) : 2101 - 2110