Inhibition of NF-κB-Dependent T Cell Activation Abrogates Acute Allograft Rejection

• Published in: The Journal of immunology (1950) 2001-11, Vol.167 (10), p.5994-6001
• Main Authors: Finn, Patricia W., Stone, James R., Boothby, Mark R., Perkins, David L.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.10.5994

Using a heterotopic model of transplantation, we investigated the role of T cell activation in vivo during allograft rejection in I-κB(ΔN)-transgenic mice that express a transdominant inhibitor of NF-κB in T cells. Our results show indefinite prolongation of graft survival in the I-κB(ΔN)-transgenic recipients. Interestingly, at the time of rejection of grafts in wild-type recipients, histology of grafts in the I-κB(ΔN)-transgenic recipients showed moderate rejection; nevertheless, grafts in the I-κB(ΔN) recipients survived >100 days. Analysis of acute phase cytokines, chemokine, chemokine receptors, and immune responses shows that the blockade of NF-κB activation in T cells inhibits up-regulation of many of these parameters. Interestingly, our data also suggest that the T cell component of the immune response exerted positive feedback regulation on the expression of multiple chemokines that are produced predominantly by non-T cells. In conclusion, our studies indicate NF-κB activation in T cells is necessary for acute allograft rejection.