Journal article

Unlike CD4( ) T-cell help, CD28 costimulation is necessary for effective primary CD8( ) T-cell influenza-specific immunity

Shirley GK Seah, Emma M Carrington, Wy C Ng, Gabrielle T Belz, Jamie L Brady, Robyn M Sutherland, Manuela S Hancock, Nicole L La Gruta, Lorena E Brown, Stephen J Turner, Yifan Zhan, Andrew M Lew



The importance of costimulation on CD4(+) T cells has been well documented. However, primary CTLs against many infections including influenza can be generated in the absence of CD4(+) T-cell help. The role of costimulation under such "helpless" circumstances is not fully elucidated. Here, we investigated such a role for CD28 using CTLA4Ig transgenic (Tg) mice. To ensure valid comparison across the genotypes, we showed that all mice had similar naïve precursor frequencies and similar peak viral loads. In the absence of help, viral clearance was significantly reduced in CTLA4Ig Tg mice compared with WT mice. CD44(+) BrdU(+) influenza-specific CD8(+) T cells were diminished in CTLA4Ig Tg mic..

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Awarded by National Health & Medical Research Council of Australia

Awarded by Juvenile Diabetes Research Foundation

Funding Acknowledgements

We thank Dr. Ian Barr and Chris Durrant from WHO Collaborative Centre for Reference and Research on Influenza, Melbourne, for help in virus culture. This work was supported by National Health & Medical Research Council of Australia Program (#516700) and Project grants (#575543, 637324), Juvenile Diabetes Research Foundation grants (#447718), Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIIS, Pfizer Senior Research Fellowship (S. J. T.), Sylvia and Charles Viertel Fellowship (G. T. B.), and DSO National Laboratories Scholarship, Singapore (S. G. K. S.).