Role of the NF-κB transcription factor c-Rel in the generation of CD8+T-cell responses to Toxoplasma gondii

Abstract

The nuclear factor κB transcription factor c-Rel is exclusively expressed in immune cells and plays a role in numerous cellular functions including proliferation, survival and production of chemokines and cytokines. c-Rel has also been implicated in the regulation of multiple genes involved in innate and adaptive immune responses to the intracellular protozoan parasite Toxoplasma gondii, in particular IL-12. To better understand how this transcription factor controls the CD8+ T-cell response to this organism, wild-type (WT) and c-Rel-/- mice were challenged with a replication-deficient strain of T. gondii that expresses the model antigen ovalbumin (OVA). These studies revealed that c-Rel was required for optimal primary expansion of OVA-specific CD8+ T cells and that immunized c-Rel-deficient mice were susceptible to challenge with a virulent strain of T. gondii. However, when c-Rel-/- cells specific for OVA were adoptively transferred into a WT recipient, or c-Rel-/- mice were treated with IL-12 at the time of immunization, there was no apparent proliferative defect. Surprisingly, upon secondary challenge, antigen-specific CD8+ T cells in c-Rel-/- mice expanded to a much greater degree in terms of frequency as well as numbers when compared with WT mice. Despite this, the cytokine responses of c-Rel-/- mice remained defective, consistent with their susceptibility to secondary challenge. Together, these results indicate that in this infection model, the major influence of c-Rel in generation of CD8+ T-cell responses is through its regulation of the inflammatory environment, rather than playing a substantial T-cell-intrinsic role. © The Japanese Society for Immunology. 2010. All rights reserved.