Programming for CD8 T cell memory development requires IL-12 or type I IFN.
Inflammation can have both positive and negative effects on development of CD8 T cell memory, but the relative contributions and cellular targets of the cytokines involved are unclear. Using CD8 T cells lacking receptors for IL-12, type I IFN, or both, we show that these cytokines act directly on CD8 T cells to support memory formation in response to vaccinia virus and Listeria monocytogenes infections. Development of memory to vaccinia is supported predominantly by IL-12, whereas both IL-12 and type I IFN contribute to memory formation in response to Listeria. In contrast to memory formation, the inability to respond to IL-12 or type I IFN had a relatively small impact on the level of primary expansion, with at most a 3-fold reduction in the case of responses to Listeria. We further show that programming for memory development by IL-12 is complete within 3 days of the initial naive CD8 T cell response to Ag. This programming does not result in formation of a population that expresses killer cell lectin-like receptor G1, and the majority of the resulting memory cells have a CD62L(high) phenotype characteristic of central memory cells. Consistent with this, the cells undergo strong expansion upon rechallenge and provide protective immunity. These data demonstrate that IL-12 and type I IFN play an essential early role in determining whether Ag encounter by naive CD8 T cells results in formation of a protective memory population.
Xiao
Zhengguo
Z
Center for Immunology and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Casey
Kerry A
KA
Jameson
Stephen C
SC
Curtsinger
Julie M
JM
Mescher
Matthew F
MF
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D002460:Cell Line; D002478:Cells, Cultured; D007156:Immunologic Memory / Q000235:genetics; D007370:Interferon Type I / Q000378:metabolism / Q000502:physiology*; D018664:Interleukin-12 / Q000378:metabolism / Q000502:physiology*; D008089:Listeria monocytogenes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000235:genetics; D053707:Receptors, Interleukin-12 / Q000172:deficiency / Q000235:genetics; D014616:Vaccinia virus / Q000276:immunology
C508032:Ifnar1 protein, mouse; C508440:Il12rb1 protein, mouse; D007370:Interferon Type I; D053707:Receptors, Interleukin-12; D053633:Receptor, Interferon alpha-beta; D018664:Interleukin-12