Staphylococcal enterotoxin B stimulates expansion of autoreactive T cells that induce apoptosis in intestinal epithelial cells: Regulation of autoreactive responses by IL-10
K. Ito et al., Staphylococcal enterotoxin B stimulates expansion of autoreactive T cells that induce apoptosis in intestinal epithelial cells: Regulation of autoreactive responses by IL-10, J IMMUNOL, 164(6), 2000, pp. 2994-3001
T cell responses to self Ags and normal microbial flora are carefully regul
ated to prevent autoreactivity, Because IL-10-deficient mice develop coliti
s, and this response is triggered by luminal flora, we investigated whether
IL-10 regulates the ability of microbial Ags to induce autoreactive T cell
s that could contribute to intestinal inflammation, T cells from mild-type
mice were primed with staphylococcal enterotoxin B (SEB) in vitro, which in
duced an autoreactive proliferative response to syngeneic feeder cells, The
cells mere predominately CD3(+) and CD4(+), T cells from IL-10-deficient m
ice were constitutively autoreactive, and SEE priming enhanced this further
, The autoreactive, proliferative response of T cells from wild-type mice w
as 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 autore
active repertoire was expanded after SEE priming, we used CBA/J mice (Mls-1
(a)) in which autoreactive T cells recognizing the endogenous viral superan
tigen are depleted (V beta 6, 7, 8.1 TCR-bearing cells). However, SEE rescu
ed these autoreactive T cell repertoires, Adding anti-MHC class II. Ab bloc
ked the autoreactive response. SEE-primed splenic or colonic T cells also i
nduced 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 co
ntribute to epithelial cell damage.