| First Author | Lischke T | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 1 | Pages | 234-44 |
| PubMed ID | 22661090 | Mgi Jnum | J:188938 |
| Mgi Id | MGI:5442646 | Doi | 10.4049/jimmunol.1102034 |
| Citation | Lischke T, et al. (2012) Comprehensive analysis of CD4+ T cells in the decision between tolerance and immunity in vivo reveals a pivotal role for ICOS. J Immunol 189(1):234-44 |
| abstractText | We have established a comprehensive in vivo mouse model for the CD4(+) T cell response to an "innocuous" versus "dangerous" exogenous Ag and developed an in vivo test for tolerance. In this model, specific gene-expression signatures, distinctive upregulation of early T cell-communication molecules, and differential expansion of effector T cells (Teff) and regulatory T cells (Treg) were identified as central correlates of T cell tolerance and T cell immunity. Different from essentially all other T cell-activation molecules, ICOS was found to be induced in the immunity response and not by T cells activated under tolerogenic conditions. If expressed, ICOS did not act as a general T cell costimulator but selectively caused a massive expansion of effector CD4(+) T cells, leaving the regulatory CD4(+) T cell compartment largely undisturbed. Thus, ICOS strongly contributed to the dramatic change in the balance between Ag-specific Teff and Treg from approximately 1:1 at steady state to 21:1 at the height of the immune response. This newly defined role for the balance of Teff to Treg, together with its known key function in T cell help for B cells, establishes ICOS as a central mediator of immunity. Given its exceptionally selective induction on CD4(+) T cells under inflammatory, but not tolerogenic, conditions, ICOS emerges as a pivotal effector molecule in the early decision between tolerance and immunity to exogenous Ag. |
