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Bacterial superantigen staphylococcal enterotoxin B (SEB) can
cause proliferation, anergy, or deletion of specific T
cells bearing T cell receptor (TCR) Vb7, 8.1-3
domains.
Previous studies in our laboratory showed that SEB induced
apoptosis of thymocytes in BALB/c mice, whereas there was
no or little effect in B6 and other I-E- strains of mice.
Taking advantage of the differential effects of SEB in I-E+ and
I-E- mice, we investigated the parameters and
signalings involved in apoptosis following in vivo
administration of SEB. Flow cytometry analysis revealed the
expression of high level of!the cell surface receptor
Fas/APO-1 on thymocytes from both BALB/c and B6 mice,
and there was no alteration of its expression after SEB
treatment. However, the expression of the Fas-L on
thymocytes was undetectable with the similar method.
Further analysis by semiquantitative RT-PCR showing an increase
in mRNA expression of Fas-L in BALB/c mice 2 h after
SEB injection. Although B6 mice did not exert
thymus atrophy when treated by SEB, there was yet an increase in
Fas-L mRNA expression of B6 thymocytes. The
patterns of other surface markers have also been
demonstrated showing an elevation of TCRabhigh, CD3high and CD69
high on thymocytes from BALB/c but not B6,
B10 and A.BY mice. Furthermore, our data
indicated an increase in IL-2 mRNA expression 2 h after SEB
injection to BALB/c mice, and this augmentation sustained
up to 24 h. In B6 mice, the IL-2 mRNA expression
also exerted an onset at 2 h and returned to the control level
after 6 h. Flow cytometry analysis of IL-2Ra (CD25) on the
surface of thymocytes revealed an increase in BALB/c mice
which reached a maximum at 24 h, whereas in B6 mice there was
only little increase at early stage.
Interestingly, upregulation of IL-2Ra in BALB/c thymocytes
occurred in both Vb8- and non-Vb8-bearing cells, indicating that
SEB-nonresponsive cells may also be affected in the
microenvironment. Moreover, the two-stage elevation of
Nur77 mRNA was observed in BALB/c but not in B6 mice following
SEB injection. In the present study, we also showed
that MRL-lpr/lpr mice which was defective in the Fas
gene, exerted thymus atrophy after SEB administration. These
were demonstrated by the reduction in thymus weight,
thymocyte number, CD4+CD8+ subpopulation, and the
appearance of DNA fragmentation. Further studies indicated that
expression of TCRabhigh, CD3high and CD69high on
thymocytes from MRL-lpr/lpr mice show a
pattern similar to that from BALB/c mice. Taken together, the
results indicate that Fas/Fas-L interaction may not play
a major role in thymocyte apoptosis induced by SEB.
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