Synergistic Costimulation by Both B7 Molecules Regulates Colitis Pathogenesis
Article first published online: 24 AUG 2006
Annals of the New York Academy of Sciences
How to Cite
KIM, G., SCHOENBERGER, S. P., SHARPE, A. and KRONENBERG, M. (2006), Synergistic Costimulation by Both B7 Molecules Regulates Colitis Pathogenesis. Annals of the New York Academy of Sciences, 1072: 233–241. doi: 10.1196/annals.1326.012
- Issue published online: 24 AUG 2006
- Article first published online: 24 AUG 2006
Abstract: It has been reported that B7-1 and B7-2 play different roles in the pathogenesis of autoimmunity, but this issue is controversial. Here we analyzed colitis induced by transfer of CD45RBhigh CD4+ T cells to immune-deficient recipients that lack expression of either B7-1 or B7-2. Surprisingly, disease was greatly accelerated in Rag−/− recipients deficient for either B7 molecule. Antigen presenting cells (APCs) lacking B7-1 or B7-2 stimulated T cell proliferation in vitro, but caused suboptimal IL-2 production, leading to decreased induction of CTLA-4. The data suggest that regulatory T cells function relatively normally in B7 single-deficient recipients, but they cannot restrain the increased pathogenesis by naïve cells primed in B7 single-deficient mice. Therefore, the inhibitory effect of CTLA-4 on pathogenic T cells likely slows colitis, even in the absence of regulatory T cells. While a full block of costimulation may prevent autoimmunity, our data indicate, surprisingly, that a partial block may in some cases augment disease.