CD70 and IFN-1 selectively induce eomesodermin or T-bet and synergize to promote CD8+ T-cell responses

Dong, H., Franklin, N.A., Ritchea, S.B., Yagita, H., Glennie, M.J. and Bullock, T.N.J. (2015) CD70 and IFN-1 selectively induce eomesodermin or T-bet and synergize to promote CD8+ T-cell responses. European Journal of Immunology, 45 (12), 3289-3301. (doi:10.1002/eji.201445291). (PMID:26461455)

Abstract

CD70-mediated stimulation of CD27 is an important cofactor of CD4+ T-cell licensed dendritic cells (DCs). However, it is unclear how CD70-mediated stimulation of T cells is integrated with signals that emanate from signal 3 pathways, such as type-1 interferon (IFN-1) and IL-12. We find that while stimulation of CD27 in isolation drives weak EomesoderminhiT-betlo CD8+ T-cell responses to OVA immunization, profound synergistic expansion is achieved by cotargeting TLR. This cooperativity can substantially boost antiviral CD8+ T-cell responses during acute infection. Concomitant stimulation of TLR significantly increases per cell IFN-? production and the proportion of the population with characteristics of short-lived effector cells, yet also promotes the ability to form long-lived memory. Notably, while IFN-1 contributes to the expression of CD70 on DCs, the synergy between CD27 and TLR stimulation is dependent upon IFN-1's effect directly on CD8+ T cells, and is associated with the increased expression of T-bet in T cells. Surprisingly, we find that IL-12 fails to synergize with CD27 stimulation to promote CD8+ T-cell expansion, despite its capacity to drive effector CD8+ T-cell differentiation. Together, these data identify complex interactions between signal 3 and costimulatory pathways, and identify opportunities to influence the differentiation of CD8+ T-cell responses.

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