Role of the NF-κB transcription factor c-Rel in the generation of CD8+ T-cell responses to Toxoplasma gondii.
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.
Department of Pathobiology, University of Pennsylvania, 380 South University Avenue, Philadelphia, PA 19104, USA.
Kimberly A
KA
Jordan
Christopher D
CD
Dupont
Elia D
ED
Tait
Hsiou-Chi
HC
Liou
Christopher A
CA
Hunter
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020569:Proto-Oncogene Proteins c-rel / Q000172:deficiency / Q000378:metabolism*; D014122:Toxoplasma / Q000276:immunology*
D020569:Proto-Oncogene Proteins c-rel