The Journal of Experimental Medicine
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Published 19 July 2004. doi:10.1084/jem.20032229
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 2, 181-189
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Protein Kinase C {theta} Is Critical for the Development of In Vivo T Helper (Th)2 Cell But Not Th1 Cell Responses

Benjamin J. Marsland1, Timothy J. Soos2, Gerald Späth3, Dan R. Littman2, and Manfred Kopf1

1 Molecular Biomedicine, Swiss Federal Institute of Technology, CH8952 Zurich, Switzerland
2 Howard Hughes Medical Institute and Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, and 3 Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, NY 10016

Address correspondence to Manfred Kopf, Molecular Biomedicine, Swiss Federal Institute of Technology, Wagistr. 27, CH8952 Zurich-Schlieren, Switzerland. Phone: 41-1-633-6470; Fax: 41-1-633-1350; email: Manfred.Kopf{at}ethz.ch

The serine/threonine-specific protein kinase C (PKC)-{theta} is predominantly expressed in T cells and localizes to the center of the immunological synapse upon T cell receptor (TCR) and CD28 signaling. T cells deficient in PKC-{theta} exhibit reduced interleukin (IL)-2 production and proliferative responses in vitro, however, its significance in vivo remains unclear. We found that pkc-{theta}–/– mice were protected from pulmonary allergic hypersensitivity responses such as airway hyperresponsiveness, eosinophilia, and immunoglobulin E production to inhaled allergen. Furthermore, T helper (Th)2 cell immune responses against Nippostrongylus brasiliensis were severely impaired in pkc-{theta}–/– mice. In striking contrast, pkc-{theta}–/– mice on both the C57BL/6 background and the normally susceptible BALB/c background mounted protective Th1 immune responses and were resistant against infection with Leishmania major. Using in vitro TCR transgenic T cell–dendritic cell coculture systems and antigen concentration-dependent Th polarization, PKC-{theta}–deficient T cells were found to differentiate into Th1 cells after activation with high concentrations of specific peptide, but to have compromised Th2 development at low antigen concentration. The addition of IL-2 partially reconstituted Th2 development in pkc-{theta}–/– T cells, consistent with an important role for this cytokine in Th2 polarization. Taken together, our results reveal a central role for PKC-{theta} signaling during Th2 responses.

Key Words: PKC-{theta} • asthma • Leishmania • nippostrongylus • Th2 cell

B.J. Marsland and T.J. Soos contributed equally to this work.

Abbreviations used in this paper: AHR, airway hyperresponsiveness; BAL, bronchoalveolar lavage; i.n., intranasal(ly); MetCh, methacholine chloride; Nb, Nippostrongylus brasiliensis; NF, nuclear factor; PKC, protein kinase C.


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