| First Author | Marsland BJ | Year | 2004 |
| Journal | J Exp Med | Volume | 200 |
| Issue | 2 | Pages | 181-9 |
| PubMed ID | 15263025 | Mgi Jnum | J:100165 |
| Mgi Id | MGI:3587418 | Doi | 10.1084/jem.20032229 |
| Citation | Marsland BJ, et al. (2004) Protein kinase C theta is critical for the development of in vivo T helper (Th)2 cell but not Th1 cell responses. J Exp Med 200(2):181-9 |
| abstractText | 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. |
