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Cutting Edge: Tissue-Resident Memory CTL Down-Regulate Cytolytic Molecule Expression following Virus Clearance¹

Justine D. Mintern^*, Carole Guillonneau^*, Francis R. Carbone^*, Peter C. Doherty^*, and Stephen J. Turner^2,*

^* Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia; and Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105

CTL express lytic proteins that mediate the cytolysis of virus-infected cells. In this study, cytolytic transcriptional profiles were determined for individual CTL responding to influenza A virus and HSV-1. During acute infection, influenza-specific CTL in the spleen and respiratory airways displayed highly activated cytolytic profiles, as did HSV-1-specific CTL localized in the spleen, skin, and dorsal root ganglia (DRG). In contrast, memory CTL dramatically down-regulated cytolytic molecule transcription. This occurred for both lymphoid (spleen) and tissue-resident (skin and/or lung) memory CTL. In contrast, HSV-1-specific CTL localized in the dorsal root ganglia in the presence latent HSV-1 Ag did not down-regulate cytolytic molecule transcription. Therefore, both lymphoid and tissue-resident memory CTL down-regulate cytolytic molecule transcription following virus clearance unless localized Ag is present.

¹ J.D.M. was supported by a National Health and Medical Research Council (NHMRC; Australia) C. J. Martin Fellowship; C.G. was supported by a Marie Curie Outgoing International Fellowship; F.R.C. was supported by NHMRC (Australia); P.C.D. was supported by a NHMRC (Australia) Burnet Grant; and S.J.T. was supported by a NHMRC (Australia) R. D. Wright Fellowship.

² Address correspondence and reprint requests to Dr. Stephen J. Turner, Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia. E-mail address: sjturn{at}unimelb.edu.au

³ Abbreviations used in this paper: Pfp, perforin; Gzm, granzyme; DRG, dorsal root ganglia, gBT, gB-specific CTL.