Inhibition of NF-kappaB-dependent T cell activation abrogates acute allograft rejection.

Finn PW, Stone JR, Boothby MR, Perkins DL
J Immunol. 2001 167 (10): 5994-6001

PMID: 11698479 · 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-kappaB(DeltaN)-transgenic mice that express a transdominant inhibitor of NF-kappaB in T cells. Our results show indefinite prolongation of graft survival in the I-kappaB(DeltaN)-transgenic recipients. Interestingly, at the time of rejection of grafts in wild-type recipients, histology of grafts in the I-kappaB(DeltaN)-transgenic recipients showed moderate rejection; nevertheless, grafts in the I-kappaB(DeltaN) recipients survived >100 days. Analysis of acute phase cytokines, chemokine, chemokine receptors, and immune responses shows that the blockade of NF-kappaB 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-kappaB activation in T cells is necessary for acute allograft rejection.

MeSH Terms (20)

Acute-Phase Reaction Animals Chemokines Cytokines Graft Enhancement, Immunologic Graft Rejection Graft Survival I-kappa B Proteins Isoantigens Kinetics Lymphocyte Activation Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Transgenic NF-kappa B Receptors, Chemokine RNA, Messenger T-Lymphocytes

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