title: CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes.
abstract: A long-standing paradox in cellular immunology concerns the conditional requirement for CD4+ T-helper (T(H)) cells in the priming of cytotoxic CD8+ T lymphocyte (CTL) responses in vivo. Whereas CTL responses against certain viruses can be primed in the absence of CD4+ T cells, others, such as those mediated through 'cross-priming' by host antigen-presenting cells, are dependent on T(H) cells. A clearer understanding of the contribution of T(H) cells to CTL development has been hampered by the fact that most T(H)-independent responses have been demonstrated ex vivo as primary cytotoxic effectors, whereas T(H)-dependent responses generally require secondary in vitro re-stimulation for their detection. Here, we have monitored the primary and secondary responses of T(H)-dependent and T(H)-independent CTLs and find in both cases that CD4+ T cells are dispensable for primary expansion of CD8+ T cells and their differentiation into cytotoxic effectors. However, secondary CTL expansion (that is, a secondary response upon re-encounter with antigen) is wholly dependent on the presence of T(H) cells during, but not after, priming. Our results demonstrate that T-cell help is 'programmed' into CD8+ T cells during priming, conferring on these cells a hallmark of immune response memory: the capacity for functional expansion on re-encounter with antigen.
authors.affiliation: Division of Cellular Immunology and Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, California 92121, USA.
authors.forename: Edith M
authors.initials: EM
authors.lastname: Janssen
authors.forename: Edward E
authors.initials: EE
authors.lastname: Lemmens
authors.forename: Tom
authors.initials: T
authors.lastname: Wolfe
authors.forename: Urs
authors.initials: U
authors.lastname: Christen
authors.forename: Matthias G
authors.initials: MG
authors.lastname: von Herrath
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Schoenberger
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D000941:Antigens