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ß+CD4-CD8- Antigen-Specific Suppressor T Cell Clones1
*
Department of Laboratory Medicine and Pathobiology, and Multi Organ Transplant Program, Toronto Hospital Research Institute, University of Toronto, Toronto, Ontario, Canada; and
The Amgen Institute, Ontario Cancer Institute, and Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, Ontario, Canada
The regulation of apoptosis in mature CD4+ or
CD8+ 
ß+ T cells has been well studied. How
the survival and death is regulated in peripheral
CD4-CD8- (double negative, DN)
ß+ T cells remains unknown. Recent studies suggest
that peripheral DN T cells may play an important role in the regulation
of the immune responses mediated by CD4+ or
CD8+ T cells. Here, we used immunosuppressive DN T cell
clones to elucidate the mechanisms involved in the regulation of death
and survival of ß+ DN T cells. The DN T cell clones
were generated from the spleen cells of 2C transgenic mice, which
express the transgenic TCR specific for Ld and permanently
accepted Ld+ skin allografts after pretransplant infusion
of Ld+ lymphocytes. We report that 1) the mature DN T cells
are highly resistant to TCR cross-linking-induced apoptosis in the
presence of exogenous IL-4; 2) Fas/Fas-ligand and TNF-/TNFR pathways
do not play an apparent role in regulating apoptosis in DN T cells; 3)
the DN T cells constitutively express a high level of
Bcl-xL, but not Bcl-2; 4) both Bcl-xL and Bcl-2
are up-regulated following TCR-cross-linking; and 5) IL-4 stimulation
significantly up-regulates Bcl-xL and c-Jun expression and
leads to mitogen-activated protein kinase phosphorylation in DN T
cells, which may contribute to the resistance to apoptosis in these T
cells. Taken together, these results provide us with an insight into
how mature DN T cells resist activation-induced apoptosis to provide a
long-term suppressor function in vivo.
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