Establishment and recall of CD8+ T-cell memory in a model of localized transient infection.
The influenza A virus model of localized, transient respiratory infection provides a well-defined experimental system for dissecting the induction and maintenance of CD8+ T-cell memory. This review focuses on quantitative and qualitative aspects of the prominent D(b)NP366- and D(b)PA224-specific CD8+ T-cell responses in virus-infected B6 mice. The different virus-specific effector and memory sets are compared by phenotypic [CD62L, interleukin-7 receptor-alpha (IL-7Ralpha), and IL-15Rbeta expression] and functional [interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and IL-2 production] analyses. Most clonotypes [defined by T-cell receptor (TCR) CDR3beta sequence] generated during the acute phase of infection survive into memory, with those expressing the more consensus 'canonical' TCRs being the major contributors to the recall response. The extent of clonal expansion and the size of memory CD8+ T-cell populations has been characterized for mice challenged with either wildtype or mutant viruses, where broadly equivalent D(b)NP366 and D(b)PA224 expression was achieved by disabling the peptides in their native configuration, then expressing them in the viral neuraminidase protein. Combining the clonotypic and antigen dose analyses led to a somewhat mechanistic conclusion that the magnitude of any virus-specific CD8+ T-cell response will be a direct function of antigen dose and the size of the naïve or memory CD8+ T-cell precursor pool.
Kedzierska
Katherine
K
Department of Microbiology and Immunology, University of Melbourne, Parkville, Melbourne, Australia.
La Gruta
Nicole L
NL
Turner
Stephen J
SJ
Doherty
Peter C
PC
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D053646:Interleukin-2 Receptor beta Subunit; D019041:L-Selectin / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis / Q000276:immunology
C508020:IL2RB protein, human; C508022:Il2rb protein, mouse; D053646:Interleukin-2 Receptor beta Subunit; D015375:Receptors, Interleukin-2; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain; D019041:L-Selectin