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

Much of the CD8(+) T cell response in H2(b) mice with influenza pneumonia is directed at the nucleoprotein(366-374) (NP366) and acid polymerase(224-233) (PA(224)) peptides presented by the H2D(b) MHC class I glycoprotein. These (DNP366-)-N-b 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) alpha 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-gamma and TNF-alpha 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(-/-) mite, a pattern that correlates with the profiles of TNFR expression in the TNFR2(+/+) controls. Thus, it seems that TNFR2-mediated editing of nfluenza-specific 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 (DNP366-)-N-b and D(b)PA(224) epitopes cannot be considered to reflect differential TNFR2-mediated T cell editing.