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英文摘要
Staphylococcal enterotoxin B (SEB), a bacterial superantigen,
stimulates specific T cells bearing T cell receptor (TCR) Vb7,
8.1-3 domains and causes cell proliferation, anergy, or
apoptosis. Previous studies in our laboratory showed that in
vivo administration of SEB induced thymocyte apoptosis in BALB/c
(I-E+) but not in B6 (I-E-) mice. Further experiments by
treatment with anti-MHC class II monoclonal antibodies (mAb) to
BALB/c mice indicated that anti-I-Ed pretreatment inhibited SEB-
induced thymocyte apoptosis whereas anti-I-Ad exerted less
effect. Taking advantage of the differential effects of SEB in
I-E+ and I-E- mice, one may investigate the factors which are
involved in thymocyte apoptosis and further the mechanism of
apoptosis. The parameters of interest for the studies include
cytokines produced in the thymus and cell-to-cell interaction.
Previous studies in our laboratory indicated that SEB-induced
thymocyte apoptosis is related to the expression and signal
transduction of IL-2R or other cytokine receptors. Cell-to-cell
interaction involves both the interaction among thymocytes
themselves and between thymocytes and thymic stromal cells, and
the role that adhesion molecules may play is of interest for
studies. The interactions between leukocyte function-associated
antigen-1 (LFA-1) and its ligands have been suggested to be
involved in T-cell development and immune response. However,
the precise role of these molecules is not clear. In this study,
we investigated in vivo the involvement of LFA-1 and
intercellular adhesion molecule-1 (ICAM-1) in thymocyte
apoptosis induced by SEB. By flow cytometric analysis, a high
level of LFA-1 expression was observed on thymocytes from both
BALB/c and B6 mice, and its expression remained unchanged
following SEB treatment. The expression of ICAM-1 on thymocytes
was low in naive mice and slightly increased between 6 and 24 h
after SEB stimulation in BALB/c but not in B6 mice. Detection
of ICAM-1 expression in thymic organs by immunohistochemistry
revealed an earlier onset (2 h) in BALB/c mice than that in B6
mice. The ICAM-1 molecules were predominantly expressed in
nonthymic cells. To further investigate the role of LFA-1
/ICAM-1 interaction in SEB-induced thymocyte apoptosis,
anti-ICAM-1 or anti-LFA-1 mAb were given to BALB/c mice before
SEB administration. Treatment with anti-ICAM-1 or anti-LFA-1
mAb both caused an inhibition on SEB-induced cell death,
suggesting the involvement of LFA-1/ICAM-1 interaction during
thymocyte apoptosis. During the process of SEB-induced
thymocyte apoptosis, there was an increased expression of IL-2
mRNA and CD25 (IL-2Ra). The upregulation of IL-2 mRNA and CD25
expression was diminished by treatment with anti-LFA-1 mAb.
However, anti-ICAM-1 mAb treatment caused less effect. These
results suggest the differential regulation caused by LFA-1 and
ICAM-1. In summary, ICAM-1 expression is upregulated after SEB
stimulation, and the interaction of ICAM-1/LFA-1 and IL-2/IL-2R
are involved in thymocyte apoptotic process.
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