title: CD40L expression permits CD8+ T cells to execute immunologic helper functions.
abstract: CD8(+) T cells play an essential role in immunity against intracellular pathogens, with cytotoxicity being considered their major effector mechanism. However, we here demonstrate that a major part of central and effector memory CD8(+) T cells expresses CD40L, one key molecule for CD4(+) T-cell-mediated help. CD40L(+) CD8(+) T cells are detectable among human antigen-specific immune responses, including pathogens such as influenza and yellow fever virus. CD40L(+) CD8(+) T cells display potent helper functions in vitro and in vivo, such as activation of antigen-presenting cells, and exhibit a cytokine expression signature similar to CD4(+) T cells and unrelated to cytotoxic CD8(+) T cells. The broad occurrence of CD40L(+) CD8(+) T cells in cellular immunity implicates that helper functions are not only executed by major histocompatibility complex (MHC) class II-restricted CD4(+) helper T cells but are also a common feature of MHC class I-restricted CD8(+) T cell responses. Due to their versatile functional capacities, human CD40L(+) CD8(+) T cells are promising candidate cells for immune therapies, particularly when CD4(+) T-cell help or pathogen-associated molecular pattern signals are limited.
authors.affiliation: Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine, Berlin, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Frentsch
authors.forename: Regina
authors.initials: R
authors.lastname: Stark
authors.forename: Nadine
authors.initials: N
authors.lastname: Matzmohr
authors.forename: Sarah
authors.initials: S
authors.lastname: Meier
authors.forename: Sibel
authors.initials: S
authors.lastname: Durlanik
authors.forename: Axel R
authors.initials: AR
authors.lastname: Schulz
authors.forename: Ulrik
authors.initials: U
authors.lastname: Stervbo
authors.forename: Karsten
authors.initials: K
authors.lastname: Jürchott
authors.forename: Friedemann
authors.initials: F
authors.lastname: Gebhardt
authors.forename: Guido
authors.initials: G
authors.lastname: Heine
authors.forename: Morgan A
authors.initials: MA
authors.lastname: Reuter
authors.forename: Michael R
authors.initials: MR
authors.lastname: Betts
authors.forename: Dirk
authors.initials: D
authors.lastname: Busch
authors.forename: Andreas
authors.initials: A
authors.lastname: Thiel
mesh_terms: D000818:Animals; D023201:CD40 Ligand / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D016207:Cytokines; D000939:Epitopes; D023201:CD40 Ligand