HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jenkins, M. R. Articles by Turner, S. J. Search for Related Content PubMed PubMed Citation Articles by Jenkins, M. R. Articles by Turner, S. J.

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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.

This article has been cited by other articles:

				T. Juelich, E. Sutcliffe, A. Denton, Y. He, P. C. Doherty, C. Parish, S. J. Turner, D. Tremethick, and S. Rao Interplay between Chromatin Remodeling and Epigenetic Changes during Lineage-Specific Commitment to Granzyme B Expression J. Immunol., December 1, 2009; 183(11): 7063 - 7072. [Abstract] [Full Text] [PDF]

				C. Touvrey, L. Derre, E. Devevre, P. Corthesy, P. Romero, N. Rufer, and D. E. Speiser Dominant Human CD8 T Cell Clonotypes Persist Simultaneously as Memory and Effector Cells in Memory Phase J. Immunol., June 1, 2009; 182(11): 6718 - 6726. [Abstract] [Full Text] [PDF]

				J. D. Mintern, S. Bedoui, G. M. Davey, J. M. Moffat, P. C. Doherty, and S. J. Turner Transience of MHC Class I-restricted antigen presentation after influenza A virus infection PNAS, April 21, 2009; 106(16): 6724 - 6729. [Abstract] [Full Text] [PDF]

				E. L. Brincks, A. Katewa, T. A. Kucaba, T. S. Griffith, and K. L. Legge CD8 T Cells Utilize TRAIL to Control Influenza Virus Infection J. Immunol., October 1, 2008; 181(7): 4918 - 4925. [Abstract] [Full Text] [PDF]

				M. R. Jenkins, J. Mintern, N. L. La Gruta, K. Kedzierska, P. C. Doherty, and S. J. Turner Cell Cycle-Related Acquisition of Cytotoxic Mediators Defines the Progressive Differentiation to Effector Status for Virus-Specific CD8+ T Cells J. Immunol., September 15, 2008; 181(6): 3818 - 3822. [Abstract] [Full Text] [PDF]

				L. Rapetti, S. Meunier, C. Pontoux, and C. Tanchot CD4 Help Regulates Expression of Crucial Genes Involved in CD8 T Cell Memory and Sensitivity to Regulatory Elements J. Immunol., July 1, 2008; 181(1): 299 - 308. [Abstract] [Full Text] [PDF]

				N. S. Joshi and S. M. Kaech Effector CD8 T Cell Development: A Balancing Act between Memory Cell Potential and Terminal Differentiation J. Immunol., February 1, 2008; 180(3): 1309 - 1315. [Abstract] [Full Text] [PDF]

				J. D. Mintern, C. Guillonneau, F. R. Carbone, P. C. Doherty, and S. J. Turner Cutting Edge: Tissue-Resident Memory CTL Down-Regulate Cytolytic Molecule Expression following Virus Clearance J. Immunol., December 1, 2007; 179(11): 7220 - 7224. [Abstract] [Full Text] [PDF]