An IFN-gamma-dependent pathway controls stimulation of memory phenotype CD8+ T cell turnover in vivo by IL-12, IL-18, and IFN-gamma.
Unlike naive T cells, memory phenotype (CD44(high)) T cells exhibit a high background rate of turnover in vivo. Previous studies showed that the turnover of memory phenotype CD8(+) (but not CD4(+)) cells in vivo can be considerably enhanced by products of infectious agents such as LPS. Such stimulation is TCR independent and hinges on the release of type I IFNs (IFN-I) which leads to the production of an effector cytokine, probably IL-15. In this study, we describe a second pathway of CD44(high) CD8(+) stimulation in vivo. This pathway is IFN-gamma rather than IFN-I dependent and is mediated by at least three cytokines, IL-12, IL-18, and IFN-gamma. As for IFN-I, these three cytokines are nonstimulatory for purified T cells and under in vivo conditions probably act via production of IL-15.
Tough
D F
DF
Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire, United Kingdom. david.tough@jenner.ac.uk
Zhang
X
X
Sprent
J
J
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D007156:Immunologic Memory / Q000235:genetics; D016130:Immunophenotyping; D007275:Injections, Intravenous; D007370:Interferon Type I / Q000378:metabolism / Q000502:physiology; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018664:Interleukin-12 / Q000008:administration & dosage / Q000502:physiology*; D020382:Interleukin-18 / Q000502:physiology*; D008213:Lymphocyte Activation / Q000235:genetics; D008565:Membrane Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*
D007370:Interferon Type I; D020382:Interleukin-18; D008565:Membrane Proteins; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D053633:Receptor, Interferon alpha-beta; D018664:Interleukin-12; D007371:Interferon-gamma