Differential tumor necrosis factor receptor 2-mediated editing of virus-specific CD8 + effector T cells

Stephen J. Turner, Nicole L. La Gruta, John Stambas, Gabriela Diaz, Peter C. Doherty

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35 Citations (Scopus)


Much of the CD8 + T cell response in H2 b mice with influenza pneumonia is directed at the nucleoprotein 366-374 (NP 366 ) and acid polymerase 224-233 (PA 224 ) peptides presented by the H2D b MHC class I glycoprotein. These D b NP 366 - and D b PA 224 -specific T cell populations are readily analyzed by staining with tetrameric complexes of MHC + peptide (tetramers) or by cytokine production subsequent to in vitro stimulation with the cognate peptides. The D b PA 224 -specific CD8 + effector T cells make more tumor necrosis factor (TNF) α than the comparable CD8 + D b NP 366 + set, a difference reflected in the greater sensitivity of the CD8 + D b PA 224 + population to TNF receptor (TNFR) 2-mediated apoptosis under conditions of in vitro culture. Freshly isolated CD8 + D b NP 366 + and CD8 + D b PA 224 + T cells from influenza-infected TNFR2 -/- mice produce higher levels of IFN-γ and TNF-α after in vitro stimulation with peptide, although the avidity of the T cell receptor-epitope interaction does not change. Increased numbers of both CD8 + D b PA 224 + and CD8 + D b NP 366 + T cells were recovered from the lungs (but not the spleens) of secondarily challenged TNFR2 -/- mice, a pattern that correlates with the profiles of TNFR expression in the TNFR2 +/+ controls. Thus, it seems that TNFR2-mediated editing of influenzaspecific CD8 + T cells functions to limit the numbers of effectors that have localized to the site of pathology in the lung but does not modify the size of the less activated responder T cell populations in the spleen. Therefore, the massive difference in magnitude for the secondary, although not the primary, response to these D b NP 366 and D b PA 224 epitopes cannot be considered to reflect differential TNFR2-mediated T cell editing.

Original languageEnglish
Pages (from-to)3545-3550
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number10
Publication statusPublished - 9 Mar 2004
Externally publishedYes

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