title: Perforin plays an unexpected role in regulating T-cell contraction during prolonged Listeria monocytogenes infection.
abstract: After infection or vaccination, antigen-specific T cells proliferate then contract in numbers to a memory set point. T-cell contraction is observed after both acute and prolonged infections although it is unknown if contraction is regulated similarly in both scenarios. Here, we show that contraction of antigen-specific CD8(+)  and CD4(+)  T cells is markedly reduced in TNF/perforin-double deficient (DKO) mice responding to attenuated Listeria monocytogenes infection. Reduced contraction in DKO mice was associated with delayed clearance of infection and sustained T-cell proliferation during the normal contraction interval. Mechanistically, sustained T-cell proliferation mapped to prolonged infection in the absence of TNF; however, reduced contraction required the additional absence of perforin since T cells in mice lacking either TNF or perforin (singly deficient) underwent normal contraction. Thus, while T-cell contraction after acute infection is independent of peforin, a perforin-dependent pathway plays a previously unappreciated role to mediate contraction of antigen-specific CD8(+)  and CD4(+)  T cells during prolonged L. monocytogenes infection.
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Nathan W
authors.initials: NW
authors.lastname: Schmidt
authors.forename: Aaruni
authors.initials: A
authors.lastname: Khanolkar
authors.forename: Lisa
authors.initials: L
authors.lastname: Hancox
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Heusel
authors.forename: John T
authors.initials: JT
authors.lastname: Harty
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D049109:Cell Proliferation; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054353:Perforin / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D014409:Tumor Necrosis Factor-alpha; D054353:Perforin