title: Fully functional memory CD8 T cells in the absence of CD4 T cells.
abstract: The role of CD4 T cells in providing help to CD8 T cells in primary and secondary responses to infection remains controversial. Using recombinant strains of virus and bacteria expressing the same Ag, we determined the requirement for CD4 T cells in endogenous CD8 T cell responses to infection with vesicular stomatitis virus and Listeria monocytogenes (LM). Depletion of CD4 T cells had no effect on the frequency of primary or secondary vesicular stomatitis virus-specific CD8 T cells in either lymphoid or nonlymphoid tissues. In contrast, the primary LM-specific CD8 T cell response was CD4 T cell dependent. Surprisingly, the LM-specific CD8 T cell recall response was also CD4 T cell dependent, which correlated with a requirement for CD40/CD40L interactions. However, concomitant inhibition of CD40L and CD4 T cell removal revealed that these pathways may be operating independently. Importantly, despite the absence of CD4 T cells during the recall response or throughout the entire response, CD8 memory T cells were functional effectors and proliferated equivalently to their "helped" counterparts. These data call into question the contention that CD4 T cells condition memory CD8 T cells during the primary response and indicate that the principal role of CD4 T cells in generating CD8 memory cells after infection is augmentation of proliferation or survival through costimulatory signals.
authors.affiliation: Division of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Marzo
authors.forename: Vaiva
authors.initials: V
authors.lastname: Vezys
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Klonowski
authors.forename: Seung-Joo
authors.initials: SJ
authors.lastname: Lee
authors.forename: Guruprasaadh
authors.initials: G
authors.lastname: Muralimohan
authors.forename: Meagan
authors.initials: M
authors.lastname: Moore
authors.forename: David F
authors.initials: DF
authors.lastname: Tough
authors.forename: Leo
authors.initials: L
authors.lastname: Lefrançois
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology* / Q000502:physiology; D008088:Listeriosis / Q000276:immunology; D051379:Mice
chemical_list: D023201:CD40 Ligand