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Memory CD8+ T cells in heterologous antiviral immunity and immunopathology in the lung

Abstract

A potent role for memory CD8+ T cells in heterologous immunity was shown with a respiratory mucosal model of viral infection. Memory CD8+ T cells generated after lymphocytic choriomeningitis virus (LCMV) infection were functionally activated in vivo to produce interferon-γ (IFN-γ) during acute infection with vaccinia virus (VV). Some of these antigen-specific memory cells selectively expanded in number, which resulted in modulation of the original LCMV-specific T cell repertoire. In addition, there was an organ-selective compartmental redistribution of these LCMV-specific T cells during VV infection. The presence of these LCMV-specific memory T cells correlated with enhanced VV clearance, decreased mortality and marked changes in lung immunopathology. Thus, the participation of pre-existing memory T cells specific to unrelated agents can alter the dynamics of mucosal immunity and disease course in response to a pathogen.

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Figure 1: Immunity to LCMV provides protection against respiratory infections with VV.
Figure 2: Persistence of LCMV epitope–specific memory CD8+ T cells in lungs and MLNs of resting LCMV-immune mice and during i.n. VV infection.
Figure 3: Accumulation of LCMV-specific memory CD8+ T cells in different organs in the LCMV-immune mouse after i.n. challenge with VV.
Figure 4: Activation of LCMV-specific CD8+ T cells in mouse lungs early on after VV infection.
Figure 5: Enhanced lymphocytic infiltration in the lungs of LCMV-immune mice after infection with VV and the role of IFN-γ.
Figure 6: In situ detection of LCMV epitope–specific CD8+ T cells in lung tissue with NP396-specific tetramer.

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Acknowledgements

We thank S. S. Tevethia for assistance with the MHC tetramer protocols; D. M. Pardoll, J. P. Schneck and K. A. Kraemer for providing reagents, protocols and help in making IgG1 MHC dimers; and Y. Liu for technical assistance. Supported by National Institutes of Health research grants AR-35506 (to R. M. W.), AI-46578 (to L. K. S.) and Center Grant DK32520 (to I. J.). The contents of this publication are solely the responsibility of the authors and do not represent the official view of the National Institute of Health.

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Correspondence to Liisa K. Selin.

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Chen, H., Fraire, A., Joris, I. et al. Memory CD8+ T cells in heterologous antiviral immunity and immunopathology in the lung. Nat Immunol 2, 1067–1076 (2001). https://doi.org/10.1038/ni727

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