| First Author | Kim G | Year | 2007 |
| Journal | J Immunol | Volume | 178 |
| Issue | 9 | Pages | 5563-70 |
| PubMed ID | 17442938 | Mgi Jnum | J:145837 |
| Mgi Id | MGI:3836132 | Doi | 10.4049/jimmunol.178.9.5563 |
| Citation | Kim G, et al. (2007) Paradoxical effect of reduced costimulation in T cell-mediated colitis. J Immunol 178(9):5563-70 |
| abstractText | B7-1 and B7-2 play different roles in the pathogenesis of autoimmunity, but this is controversial. We analyzed colitis induced by transfer of CD45RB(high)CD4(+) T cells to RAG(-/-) recipients lacking B7-1 and/or B7-2. Surprisingly, disease was greatly accelerated in RAG(-/-) recipients deficient for either B7-1 or B7-2, especially in the B7-2(-/-) recipients. This accelerated colitis induction correlated with increased T cell division in vivo and production of Th1 cytokines. Although colitis pathogenesis following T cell transfer was inhibited in the absence of CD40L expression, CD40-CD40L interactions were not required in the B7-2(-/-) RAG(-/-) recipients. In vitro priming by APCs lacking either B7-1 or B7-2 caused decreased IL-2 production, which led to decreased CTLA-4 expression, although T cells primed in this way could respond vigorously upon restimulation by producing increased IL-2 and proinflammatory cytokines. Consistent with this mechanism, we demonstrate that blocking IL-2 early after T cell transfer accelerated colitis. Our data therefore outline a mechanism whereby synergistic costimulation by B7-1 and B7-2 molecules during priming is required for optimal IL-2 production. The consequent inhibitory effect of full CTLA-4 expression, induced by IL-2, may slow colitis, even in the absence of regulatory T cells. |
