title: CD4+ and CD8+ T cell- and IL-17-mediated protection against Entamoeba histolytica induced by a recombinant vaccine.
abstract: Amebiasis in the murine model can be prevented by vaccination with the Gal/GalNAc lectin through a T cell-dependent mechanism. In this work we further decipher the mechanism of this protection. Mice vaccinated with the recombinant "LecA" fragment of the Gal/GalNAc lectin with alum were capable of transferring protection to naïve recipients by both CD4+ T cells and surprisingly CD8+ T cells. We then examined the cytokine profile of these cells. CD4+ T cells from PBMC of LecA-alum vaccinated mice were observed to be a major source of IFN-γ, known to be a protective cytokine with this vaccine. In contrast, CD8+ T cells produced relatively little IFN-γ but more IL-17 than the CD4 compartment. We thus examined the role of IL-17 in vaccine mediated protection and found through neutralization experiments that this cytokine contributed to LecA-alum vaccine protection. In addition we examined whether these cells exhibited direct amebicidal activity in vitro and found that both populations had amebicidal activity at high concentrations (1000:1) but CD8+ T cells appeared more potent, capable of cytotoxicity at a 100:1 ratio. In conclusion, both CD4 and CD8 T cells exert protection with this amebiasis vaccine. The mechanism of CD8 T cell-mediated protection may include direct amebicidal activity and/or IL-17 production. Both IL-17 and IFN-γ are useful surrogates for immune protection.
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Xiaoti
authors.initials: X
authors.lastname: Guo
authors.forename: Lisa
authors.initials: L
authors.lastname: Barroso
authors.forename: David M
authors.initials: DM
authors.lastname: Lyerly
authors.forename: William A
authors.initials: WA
authors.lastname: Petri
authors.forename: Eric R
authors.initials: ER
authors.lastname: Houpt
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002470:Cell Survival; D004748:Entamoeba histolytica / Q000276:immunology / Q000502:physiology; D004749:Entamoebiasis / Q000276:immunology / Q000517:prevention & control*; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology*; D008297:Male; D051379:Mice; D016052:Protozoan Vaccines / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D020381:Interleukin-17; D016052:Protozoan Vaccines; D014614:Vaccines, Synthetic; D007371:Interferon-gamma