An extrafollicular pathway for the generation of effector CD8+ T cells driven by the proinflammatory cytokine, IL-12

Elife. 2015 Aug 5;4. doi: 10.7554/eLife.09017. [Epub ahead of print]

Shah S1, Grotenbreg GM2, Rivera A1, Yap GS1.

Author information

Abstract

The proinflammatory cytokine IL-12 drives the generation of terminally differentiated KLRG1+ effector CD8+ T cells. Using a Toxoplasma vaccination model, we delineate the sequence of events that naïve CD8+ T cells undergo to become terminal effectors and the differentiation steps controlled by IL-12. We demonstrate that direct IL-12 signaling on CD8+ T cells is essential for the induction of KLRG1 and IFN-γ, but the subsequent downregulation of CXCR3 is controlled by IL-12 indirectly through the actions of IFN-γ and IFN-γ-inducible chemokines. Differentiation of nascent effectors occurs in an extrafollicular splenic compartment and is driven by late IL-12 production by DCs distinct from the classical CD8α+ DC. Unexpectedly, we also found extensive proliferation of both KLRG1- and KLRG1+ CD8+ T cells in the marginal zone and red pulp, which ceases prior to the final KLRG1Hi CXCR3Lo stage. Our findings highlight the notion of an extrafollicular pathway for effector T cell generation.

KEYWORDS: 

CD8 T cells; Toxoplasma; effector cells; extrafollicular; immunology; infectious disease; interleukin-12; microbiology; mouse; myeloid DC

PMID:

 

26244629

 

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