| First Author | Gurung P | Year | 2009 |
| Journal | J Immunol | Volume | 183 |
| Issue | 10 | Pages | 6114-23 |
| PubMed ID | 19841180 | Mgi Jnum | J:157192 |
| Mgi Id | MGI:4430154 | Doi | 10.4049/jimmunol.0901676 |
| Citation | Gurung P, et al. (2009) Activation-induced CD154 expression abrogates tolerance induced by apoptotic cells. J Immunol 183(10):6114-23 |
| abstractText | The decision to generate a productive immune response or tolerance often depends on the context in which T cells first see Ag. Using a classical system of tolerance induction, we examined the immunological consequence of Ag encountered in the presence of naive or activated apoptotic cells. Naive apoptotic cells induced tolerance when injected i.v.; however, previously activated apoptotic cells induced immunity. Further analysis revealed a key role for CD154, as tolerance resulted after i.v. injection of either naive or activated apoptotic CD154(-/-) T cells, while coinjection of an agonistic anti-CD40 mAb with naive apoptotic T cells induced robust immunity. Dendritic cells fed activated apoptotic T cells in vitro produced IL-12p40 in a CD154-dependent manner, and the use of IL-12p40(-/-) mice or mAb-mediated neutralization of IL-12 revealed a link between CD154, IL-12, and the ability of activated apoptotic T cells to induce immunity rather than tolerance. Collectively, these results show that CD154 expression on apoptotic T cells can determine the outcome of an immune response to Ag recognized within the context of the apoptotic cells and suggest that the balance between naive and activated apoptotic T cells may dictate whether a productive immune response is encouraged. |
