Article: article from journal or magazin.
Protein kinase C theta is critical for the development of in vivo T helper (Th)2 cell but not Th1 cell responses.
Journal of Experimental Medicine
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.
Animals, Antigens, CD28/biosynthesis, Bronchoalveolar Lavage Fluid, Cell Differentiation, Cell Division, Cell Separation, Coculture Techniques, Cytokines/metabolism, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Interferon-gamma/metabolism, Interleukin-2/metabolism, Interleukin-4/metabolism, Isoenzymes/metabolism, Isoenzymes/physiology, Leishmania major/metabolism, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Peptides/chemistry, Protein Kinase C/metabolism, Protein Kinase C/physiology, Receptors, Antigen, T-Cell/metabolism, Signal Transduction, Th1 Cells/metabolism, Th2 Cells/metabolism, Transgenes
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