Heterogeneity of effector phenotype for acute phase and memory influenza A virus-specific CTL.
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(b)NP(366)- or D(b)PA(224)-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.
Jenkins
Misty R
MR
Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.
Kedzierska
Katherine
K
Doherty
Peter C
PC
Turner
Stephen J
SJ
D000208:Acute Disease; D000818:Animals; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens / Q000096:biosynthesis / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D007156:Immunologic Memory; D016130:Immunophenotyping; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000096:biosynthesis / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000276:immunology; D012324:RNA-Dependent RNA Polymerase / Q000096:biosynthesis / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000276:immunology* / Q000821:virology*; D014758:Viral Core Proteins / Q000096:biosynthesis / Q000276:immunology; D014764:Viral Proteins / Q000096:biosynthesis / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; C061290:PA protein, influenza viruses; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase