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Heterogeneity of Effector Phenotype for Acute Phase and Memory Influenza A Virus-Specific CTL¹

Misty R. Jenkins^2,*, Katherine Kedzierska, Peter C. Doherty^*, and Stephen J. Turner^3,*

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

Ag-specific, CD8⁺ CTLs clear influenza A viruses from the lung via granzyme (Gzm) and perforin-dependent mechanisms. Ex vivo analysis of perforin-Gzm mRNA profiles demonstrated substantial heterogeneity in patterns of effector mRNA transcription of CD8⁺ D^bNP₃₆₆- or D^bPA₂₂₄-specific CTL. The only difference between the two epitope-specific sets was apparent very early after infection with similar molecular profiles seen in peak primary and secondary responses and in long-term memory. Surprisingly, memory T cells also expressed a diverse pattern of effector mRNA profile with an emphasis on GzmB and, surprisingly, GzmK. This analysis thus defines how naive, effector, and memory T cells differ in cytotoxic potential and provides novel insight into the molecular signatures of effector molecules observed at various stages after infection.

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¹ This work was supported by an Australian Postgraduate Scholarship (to M.R.J.), a National Health and Medical Research Council Burnet Award (to P.C.D.), a Victorian Government Science, Technology and Innovation Grant (to P.C.D.), an National Health and Medical Research Council Peter Doherty Postdoctoral Fellowship (to K.K.), an National Health and Medical Research Council R. D. Wright Fellowship (to S.J.T.), and a Melbourne University Early Career Researcher Grant (to S.J.T.).

² Current address: Sir William Dunn School of Pathology, University of Oxford, Oxford, U.K.

³ Address correspondence and reprint requests to Dr. Stephen J. Turner, Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia. E-mail address: sjturn{at}unimelb.edu.au

⁴ Abbreviations used in this paper: Pfp, perforin; Gzm, granzyme; NP, nucleoprotein; PA, acid polymerase; i.n., intranasally; BAL, bronchoalveolar lavage; MFI, mean fluorescence intensity.

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