Abstract
B and T lymphocyte attenuator (BTLA) is a negative regulator of T cell activation, but its function in vivo is not well characterized. Here we show that mice deficient in full-length BTLA or its ligand, herpesvirus entry mediator, had increased number of memory CD8+ T cells. The memory CD8+ T cell phenotype resulted from a T cell–intrinsic perturbation of the CD8+ T cell pool. Naive BTLA-deficient CD8+ T cells were more efficient than wild-type cells at generating memory in a competitive antigen-specific system. This effect was independent of the initial expansion of the responding antigen-specific T cell population. In addition, BTLA negatively regulated antigen-independent homeostatic expansion of CD4+ and CD8+ T cells. These results emphasize two central functions of BTLA in limiting T cell activity in vivo.
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Acknowledgements
We thank P. Aliahmad and M. Fung for critically reviewing this manuscript, S. Freigang and J.T. Tan for discussion; N. Sanathara and O. Goularte for technical assistance; and the Department of Animal Resources and the Flow Cytometry Core Facility at The Scripps Research Institute for support. Supported by the National Institutes of Health (AI-31231 to J.K.), and the Swiss National Science Foundation and the Novartis Foundation (to O.B.). This is manuscript 18376 from the Scripps Research Institute.
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C.K. and O.B. did the experiments; C.K., O.B. and J.K. designed the experiments, interpreted the results and wrote the manuscript; and Y.-X.F. contributed reagents and helped with the manuscript.
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Supplementary information
Supplementary Fig. 1
BTLA and HVEM expression on CD8+ T cell subsets. (PDF 59 kb)
Supplementary Fig. 2
Increased CD4 to CD8 T cell ratio in BTLA-KO and HVEM-KO mice. (PDF 63 kb)
Supplementary Fig. 3
BTLA expression on homeostatically expanded WT CD8+ OT-I Tg T cells. (PDF 67 kb)
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Krieg, C., Boyman, O., Fu, YX. et al. B and T lymphocyte attenuator regulates CD8+ T cell–intrinsic homeostasis and memory cell generation. Nat Immunol 8, 162–171 (2007). https://doi.org/10.1038/ni1418
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DOI: https://doi.org/10.1038/ni1418
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