CD99 Engagement on Human Peripheral Blood T Cells Results in TCR/CD3-Dependent Cellular Activation and Allows for Th1-Restricted Cytokine Production
Author:
Waclavicek Martina1, Majdic Otto1, Stulnig Thomas2, Berger Markus2, Sunder-Plassmann Raute3, Zlabinger Gerhard J.1, Baumruker Thomas4, Stöckl Johannes1, Ebner Christof5, Knapp Walter1, Pickl Winfried F.1
Affiliation:
1. *Institute of Immunology, University of Vienna, Vienna Austria; 2. †Division of Endocrinology and 3. ‡Division of Nephrology and Dialysis, Department of Internal Medicine III, 4. ¶Novartis Research Institute, Vienna, Austria 5. §Institute of General and Experimental Pathology, University of Vienna, Vienna, Austria; and
Abstract
AbstractWe 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-α and IFN-γ after this treatment. In contrast, Th2 clones were unable to produce IL-4 or IFN-γ 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.
Publisher
The American Association of Immunologists
Subject
Immunology,Immunology and Allergy
Reference64 articles.
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