title: Short-lived effector CD8 T cells induced by genetically attenuated malaria parasite vaccination express CD11c.
abstract: Vaccination with a single dose of genetically attenuated malaria parasites can induce sterile protection against sporozoite challenge in the rodent Plasmodium yoelii model. Protection is dependent on CD8(+) T cells, involves perforin and gamma interferon (IFN-γ), and is correlated with the expansion of effector memory CD8(+) T cells in the liver. Here, we have further characterized vaccine-induced changes in the CD8(+) T cell phenotype and demonstrated significant upregulation of CD11c on CD3(+) CD8b(+) T cells in the liver, spleen, and peripheral blood. CD11c(+) CD8(+) T cells are predominantly CD11a(hi) CD44(hi) CD62L(-), indicative of antigen-experienced effector cells. Following in vitro restimulation with malaria-infected hepatocytes, CD11c(+) CD8(+) T cells expressed inflammatory cytokines and cytotoxicity markers, including IFN-γ, tumor necrosis factor alpha (TNF-α), interleukin-2 (IL-2), perforin, and CD107a. CD11c(-) CD8(+) T cells, on the other hand, expressed negligible amounts of all inflammatory cytokines and cytotoxicity markers tested, indicating that CD11c marks multifunctional effector CD8(+) T cells. Coculture of CD11c(+), but not CD11c(-), CD8(+) T cells with sporozoite-infected primary hepatocytes significantly inhibited liver-stage parasite development. Tetramer staining for the immunodominant circumsporozoite protein (CSP)-specific CD8(+) T cell epitope demonstrated that approximately two-thirds of CSP-specific cells expressed CD11c at the peak of the CD11c(+) CD8(+) T cell response, but CD11c expression was lost as the CD8(+) T cells entered the memory phase. Further analyses showed that CD11c(+) CD8(+) T cells are primarily KLRG1(+) CD127(-) terminal effectors, whereas all KLRG1(-) CD127(+) memory precursor effector cells are CD11c(-) CD8(+) T cells. Together, these results suggest that CD11c marks a subset of highly inflammatory, short-lived, antigen-specific effector cells, which may play an important role in eliminating infected hepatocytes.
authors: Seattle Biomedical Research Institute, Seattle, Washington, USA.
authors: Laura A
authors: LA
authors: Cooney
authors: Megha
authors: M
authors: Gupta
authors: Sunil
authors: S
authors: Thomas
authors: Sebastian
authors: S
authors: Mikolajczak
authors: Kimberly Y
authors: KY
authors: Choi
authors: Claire
authors: C
authors: Gibson
authors: Ihn K
authors: IK
authors: Jang
authors: Sam
authors: S
authors: Danziger
authors: John
authors: J
authors: Aitchison
authors: Malcolm J
authors: MJ
authors: Gardner
authors: Stefan H I
authors: SH
authors: Kappe
authors: Ruobing
authors: R
authors: Wang
mesh_terms: D000818:Animals; D001769:Blood / Q000276:immunology; D039521:CD11c Antigen / Q000096:biosynthesis*; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D005260:Female; D016130:Immunophenotyping; D008099:Liver / Q000276:immunology; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010967:Plasmodium yoelii / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D039521:CD11c Antigen; D017780:Malaria Vaccines; D014613:Vaccines, Attenuated
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