An in vivo cytotoxicity threshold for influenza A virus-specific effector and memory CD8+ T cells
Stambas, John, Doherty, Peter C. and Turner, Stephen J. 2007, An in vivo cytotoxicity threshold for influenza A virus-specific effector and memory CD8+ T cells, The Journal of Immunology, vol. 178, no. 3, pp. 1285-1292.
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An in vivo cytotoxicity threshold for influenza A virus-specific effector and memory CD8+ T cells
Influenza A virus infection of C57BL/6 (B6) mice is characterized by prominent CD8 T cell responses to H2Db complexed with peptides from the viral nucleoprotein (NP366, ASNENMETM) and acid polymerase (PA224, SSLENFRAYV). An in vivo cytotoxicity assay that depends on the adoptive transfer of peptide-pulsed, syngeneic targets was used in this study to quantitate the cytotoxic potential of DbNP366- and DbPA224-specific acute and memory CD8 T cells following primary or secondary virus challenge. Both T cell populations displayed equivalent levels of in vivo effector function when comparable numbers were transferred into naive B6 hosts. Cytotoxic activity following primary infection clearly correlated with the frequency of tetramer-stained CD8 T cells. This relationship looked, however, to be less direct following secondary exposure, partly because the numbers of CD8DbNP366 T cells were greatly in excess. However, calculating the in vivo E:T ratios indicated that in vivo lysis, like many other biological functions, is threshold dependent. Furthermore, the capacity to eliminate peptide-pulsed targets was independent of the differentiation state (i.e., primary or secondary effectors) and was comparable for the two T cell specificities that were analyzed. These experiments provide insights that may be of value for adoptive immunotherapy, where careful consideration of both the activation state and the number of effector cells is required.
Language
eng
Field of Research
110804 Medical Virology
Socio Economic Objective
970111 Expanding Knowledge in the Medical and Health Sciences