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CD70 and IFN-1 selectively induce eomesodermin or T-bet and synergize to promote CD8+ T-cell responses.
- Source :
- European Journal of Immunology; Dec2015, Vol. 45 Issue 12, p3289-3301, 13p
- Publication Year :
- 2015
-
Abstract
- CD70-mediated stimulation of CD27 is an important cofactor of CD4<superscript>+</superscript> 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 Eomesodermin<superscript>hi</superscript>T-bet<superscript>lo</superscript> CD8<superscript>+</superscript> T-cell responses to OVA immunization, profound synergistic expansion is achieved by cotargeting TLR. This cooperativity can substantially boost antiviral CD8<superscript>+</superscript> T-cell responses during acute infection. Concomitant stimulation of TLR significantly increases per cell IFN-γ 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<superscript>+</superscript> 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<superscript>+</superscript> T-cell expansion, despite its capacity to drive effector CD8<superscript>+</superscript> T-cell differentiation. Together, these data identify complex interactions between signal 3 and costimulatory pathways, and identify opportunities to influence the differentiation of CD8<superscript>+</superscript> T-cell responses. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00142980
- Volume :
- 45
- Issue :
- 12
- Database :
- Complementary Index
- Journal :
- European Journal of Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 111429458
- Full Text :
- https://doi.org/10.1002/eji.201445291