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The Journal of Immunology, 1998, 161: 4671-4678.
Copyright © 1998 by The American Association of Immunologists

CD99 Engagement on Human Peripheral Blood T Cells Results in TCR/CD3-Dependent Cellular Activation and Allows for Th1-Restricted Cytokine Production1

Martina Waclavicek*, Otto Majdic*, Thomas Stulnig{dagger}, Markus Berger{dagger}, Raute Sunder-Plassmann{ddagger}, Gerhard J. Zlabinger*, Thomas Baumruker, Johannes Stöckl*, Christof Ebner§, Walter Knapp* and Winfried F. Pickl2,*

* Institute of Immunology, University of Vienna, Vienna Austria; {dagger} Division of Endocrinology and {ddagger} 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-{alpha} and IFN-{gamma} after this treatment. In contrast, Th2 clones were unable to produce IL-4 or IFN-{gamma} 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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