title: Multiple mechanisms compensate to enhance tumor-protective CD8(+) T cell response in the long-term despite poor CD8(+) T cell priming initially: comparison between an acute versus a chronic intracellular bacterium expressing a model antigen.
abstract: We evaluated CD8(+) T cell responses against the dominant CTL epitope, OVA(257-264), expressed by an acute (Listeria monocytogenes (LM) OVA) vs a chronic pathogen (Mycobacterium bovis bacillus Calmette-Guérin (BCG) OVA) to reveal the influence on CD8(+) T cell memory and consequent protection against a challenge with OVA-expressing tumor cells. Infection with lower doses of both pathogens resulted in stronger bacterial growth but weaker T cell memory indicating that memory correlates with pathogen dose but not with bacterial expansion. The CD8(+) T cell response induced by LM-OVA was helper T cell-independent and was characterized by a rapid effector response followed by a rapid, but massive, attrition. In contrast, BCG-OVA induced a delayed and weak response that was compensated for by a longer effector phase and reduced attrition. This response was partly dependent on CD4(+) T cells. CD8(+) T cell response induced by BCG-OVA, but not LM-OVA, was highly dependent on pathogen persistence to compensate for the weak initial CD8(+) T cell priming. Despite a stronger initial T cell response with LM-OVA, BCG-OVA provided more effective tumor (B16OVA) control at both local and distal sites due to the induction of a persistently activated acquired, and a more potent innate, immunity.
authors.affiliation: Laboratory of Cellular Immunology, Institute for Biological Sciences, National Research Council, Ottawa, Ontario, Canada.
authors.forename: Renu
authors.initials: R
authors.lastname: Dudani
authors.forename: Yvan
authors.initials: Y
authors.lastname: Chapdelaine
authors.forename: Henk van
authors.initials: Hv
authors.lastname: Faassen Hv
authors.forename: Dean K
authors.initials: DK
authors.lastname: Smith
authors.forename: Hao
authors.initials: H
authors.lastname: Shen
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Krishnan
authors.forename: Subash
authors.initials: S
authors.lastname: Sad
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D007156:Immunologic Memory; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000517:prevention & control*; D010047:Ovalbumin / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology
chemical_list: D010446:Peptide Fragments; D010047:Ovalbumin