Protein kinase C θ is critical for the development of in vivo T helper (Th)2 cell but not Th-1 cell responses

Benjamin J. Marsland, Timothy J. Soos, Gerald Späth, Dan R. Littman, Manfred Kopf

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180 Citations (Scopus)

Abstract

The serine/threonine-specific protein kinase C (PKC)-θ 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-θ exhibit reduced interleukin (IL)-2 production and proliferative responses in vitro, however, its significance in vivo remains unclear. We found that pkc-θ-/- 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-θ-/- mice. In striking contrast, pkc-θ-/- 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-θ-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-θ-/- T cells, consistent with an important role for this cytokine in Th2 polarization. Taken together, our results reveal a central role for PKC-θ signaling during Th2 responses.

Original languageEnglish
Pages (from-to)181-189
Number of pages9
JournalJournal of Experimental Medicine
Volume200
Issue number2
DOIs
Publication statusPublished - 19 Jul 2004
Externally publishedYes

Keywords

  • Asthma
  • Leishmania
  • Nippostrongylus
  • PKC-θ
  • Th2 cell

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