1. Perforin plays an unexpected role in regulating T-cell contraction during prolonged Listeria monocytogenes infection.
- Author
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Schmidt NW, Khanolkar A, Hancox L, Heusel JW, and Harty JT
- Subjects
- Animals, CD4-Positive T-Lymphocytes microbiology, CD8-Positive T-Lymphocytes microbiology, Cell Proliferation, Flow Cytometry, Immunologic Memory immunology, Listeriosis microbiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Specific Pathogen-Free Organisms, Tumor Necrosis Factor-alpha immunology, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Listeria monocytogenes immunology, Listeriosis immunology, Perforin immunology
- 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., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2012
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