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*
Institute of Immunology, University of Vienna, Vienna Austria;
Division of Endocrinology and
Division of Nephrology and Dialysis, Department of Internal Medicine III,
§
Institute of General and Experimental Pathology, University of Vienna, Vienna, Austria; and
¶
Novartis Research Institute, Vienna, Austria
We have assessed the functional effect of CD99 engagement on
resting human peripheral blood (PB) T cells. CD99, as detected by the
mAb 3B2/TA8, is constitutively expressed on all PB T cells and becomes
further up-regulated upon cellular activation. In this study we
demonstrate that cross-linking of the CD99 molecule with the agonistic
mAb 3B2/TA8 cooperates with suboptimal TCR/CD3 signals, but not with
phorbol ester, ionomycin, or CD28 mAb stimulation, to induce
proliferation of resting PB T cells. Comparable stimulatory effects
were observed with the CD99 mAb 12E7. Characterization of the signaling
pathways involved revealed that CD99 engagement leads to the elevation
of intracellular Ca2+, which is dependent on the cell
surface expression of the TCR/CD3 complex. No CD99 mAb-induced calcium
mobilization was observed on TCR/CD3-modulated or TCR/CD3-negative T
cells. To examine the impact of CD99 stimulation on subsequent cytokine
production by T cells, we cross-linked CD99 molecules in the presence
of a suboptimal TCR/CD3 trigger followed by determination of
intracellular cytokine levels. Significantly, T cell lines as well as
Th1 and Th0 clones synthesized TNF-
and IFN-
after this
treatment. In contrast, Th2 clones were unable to produce IL-4 or
IFN-
when stimulated in a similar fashion. We conclude that CD99 is
a receptor that mediates TCR/CD3-dependent activation of resting PB T
cells and specifically induces Th1-type cytokine production in
polyclonally activated T cell lines, Th1 and Th0
clones.
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