| First Author | Van Deusen KE | Year | 2010 |
| Journal | J Leukoc Biol | Volume | 87 |
| Issue | 3 | Pages | 477-85 |
| PubMed ID | 19952354 | Mgi Jnum | J:158863 |
| Mgi Id | MGI:4440728 | Doi | 10.1189/jlb.0809535 |
| Citation | Van Deusen KE, et al. (2010) CD70 expression by dendritic cells plays a critical role in the immunogenicity of CD40-independent, CD4+ T cell-dependent, licensed CD8+ T cell responses. J Leukoc Biol 87(3):477-85 |
| abstractText | The stimulation of DC by CD4(+) T cells is known to condition DC to activate naive CD8(+) T cells, predominantly via CD40-CD40L interactions. It has been proposed that a critical consequence of DC conditioning is the induction of CD70 expression. Whether and how CD70 induction contributes to CD8(+) T cell responses in the absence of CD40-CD40L interactions are unknown. CD8(+) T cell responses to adenoviral- or DC-based immunization of CD40-deficient mice revealed a CD40-independent, CD4(+) T cell-dependent pathway for CD70 induction on conventional DC. This pathway and subsequent CD8(+) T cell responses were enhanced by, but not dependent on, concomitant activation of TLR and in part, used TRANCE and LIGHT/LTalphabeta stimulation. Blocking TRANCE and LIGHT/LTalphabeta during stimulation reduced the immunogenicity of CD40-deficient DC. These data support the hypothesis that induction of CD70 expression on DC after an encounter with activated CD4(+) T cells is a major component of CD4(+) T cell-mediated licensing of DC. Further, multiple pathways exist for CD4(+) T cells to elicit CD70 expression on DC. These data in part explain the capacity of CD40-deficient mice to mount CD8(+) T cell responses and may provide additional targets for immunotherapy in situations when CD40-mediated licensing is compromised. |
