Cognate CD4+ T cell licensing of dendritic cells in CD8+ T cell immunity

CM Smith, NS Wilson, J Waithman, JA Villadangos… - Nature …, 2004 - nature.com
CM Smith, NS Wilson, J Waithman, JA Villadangos, FR Carbone, WR Heath, GT Belz
Nature immunology, 2004nature.com
Several studies have indicated that CD8+ T cells require CD4+ T cell help for memory
formation. Evidence suggests that such help can be antigen independent, challenging
whether the'licensing'of dendritic cells (DCs) by CD4+ T cells is ever required for cytotoxic T
lymphocyte (CTL) responses. We show here that help is essential for the generation of CTL
immunity to herpes simplex virus 1 and that CD4+ T cells mediate help in a cognate, antigen-
specific way. We provide direct in vivo evidence for DC licensing by helper T cells and show …
Abstract
Several studies have indicated that CD8+ T cells require CD4+ T cell help for memory formation. Evidence suggests that such help can be antigen independent, challenging whether the 'licensing' of dendritic cells (DCs) by CD4+ T cells is ever required for cytotoxic T lymphocyte (CTL) responses. We show here that help is essential for the generation of CTL immunity to herpes simplex virus 1 and that CD4+ T cells mediate help in a cognate, antigen-specific way. We provide direct in vivo evidence for DC licensing by helper T cells and show that licensing is rapid and essential for the formation of effector and memory CTLs. In situations in which DCs are poorly licensed by pathogen-derived signals, our findings suggest that CTL immunity may be heavily dependent on cognate DC licensing.
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