Journal article
Context-Dependent Role for T-bet in T Follicular Helper Differentiation and Germinal Center Function following Viral Infection
AA Sheikh, L Cooper, M Feng, F Souza-Fonseca-Guimaraes, F Lafouresse, BC Duckworth, ND Huntington, JJ Moon, M Pellegrini, SL Nutt, GT Belz, KL Good-Jacobson, JR Groom
Cell Reports | CELL PRESS | Published : 2019
Abstract
Following infection, inflammatory cues upregulate core transcriptional programs to establish pathogen-specific protection. In viral infections, T follicular helper (TFH) cells express the prototypical T helper 1 transcription factor T-bet. Several studies have demonstrated essential but conflicting roles for T-bet in TFH biology. Understanding the basis of this controversy is crucial, as modulation of T-bet expression instructs TFH differentiation and ultimately protective antibody responses. Comparing influenza and LCMV viral infections, we demonstrate that the role of T-bet is contingent on the environmental setting of TFH differentiation, IL-2 signaling, and T cell competition. Furthermor..
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Awarded by CSL Behring
Funding Acknowledgements
We thank members of the Groom lab for technical assistance and Leisa-Rebecca Watson, who performed initial experiments. This work was supported by National Health and Medical Research Council (NHMRC) project grants to J.R.G. and K.L.G.-J. (GNT1137989 and GNT1057707) and to M.P. (GNT1006592, GNT1045549, and GNT1065626) and by NIH grants to J.J.M. (R01 AI107020 and R21 AI124143). A.A.S. and B.C.D. are supported by a University of Melbourne research scholarship. J.R.G. is supported by an Australian Research Council Future Fellowship (FT130100708). K.L.G.-J. is supported by an NHMRC Career Development Fellowship (1108066). G.T.B. and S.L.N. are supported by an NHMRC Senior Principal Research Fellowship. K.L.G.-J. and M.P. are supported by Bellberry-Viertel and Sylvia & Charles Viertel Senior Medical Research Fellowships. L.C. received a Biomedicine Discovery Institute Scholarship from Monash University. F.L. is supported by a Walter and Eliza Hall Centenary Fellowship sponsored by CSL. This work was made possible through Victorian State Government Operational Infrastructure Support and the Australian Government NHMRC Independent Research Institute Infrastructure Support Scheme (IRIISS).