| First Author | Shah S | Year | 2015 |
| Journal | Elife | Volume | 4 |
| PubMed ID | 26244629 | Mgi Jnum | J:226557 |
| Mgi Id | MGI:5697757 | Doi | 10.7554/eLife.09017 |
| Citation | Shah S, et al. (2015) An extrafollicular pathway for the generation of effector CD8(+) T cells driven by the proinflammatory cytokine, IL-12. Elife 4 |
| abstractText | 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 naive 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-gamma, but the subsequent downregulation of CXCR3 is controlled by IL-12 indirectly through the actions of IFN-gamma and IFN-gamma-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 CD8alpha(+) 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 KLRG1(Hi) CXCR3(Lo) stage. Our findings highlight the notion of an extrafollicular pathway for effector T cell generation. |
