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Homeostasis and anergy of CD4+CD25+ suppressor T cells in vivo

Nature Immunology volume 3, pages 33–41 (2002)Cite this article

Abstract

CD4+CD25+ suppressor T (TS) cells play a critical role in the maintenance of peripheral tolerance. We examined here proliferative and functional responses as well as differential gene expression in TS cells. We found that TS cells were hyporesponsive to antigenic stimuli in vivo and unable to flux Ca2+ upon T cell receptor (TCR) engagement. However, TS cells were not impaired in their proliferative response to lymphopenia, which was dependent on major histocompatibility complex class II expression. Homeostatic proliferation did not abolish TS cell anergy; rather, it substantially augmented TS cell function. DNA array analyses identified genes that may inhibit responsiveness at a number of levels in multiple signaling cascades in TS cells, as well as several anti-apoptotic genes that may mediate their survival.

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Figure 1: TS cells are hyporesponsive to strong antigenic stimuli in vitro and in vivo.
Figure 2: TS cells are refractory to lymphoid chemokine–induced migration.
Figure 3: TS cells do not flux calcium.
Figure 4: CD4+CD25+ T cells require MHC class II for homeostatic expansion.
Figure 5: CD4+CD25+ and CD4+CD25− T cells acquire a similar cell surface phenotype after homeostatic proliferation, whereas TS cell suppressor function is enhanced.
Figure 6: Regulation of multiple signaling pathways in CD4+CD25+ TS cells.

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Acknowledgements

We thank K. Allen for FACS expertise, C. Plata for excellent animal care and M. Bevan, M. Bix and C. Dong for critically reviewing the manuscript. Supported by grants from the Howard Hughes Medical Institute and the National Institutes of Health.

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  1. Howard Hughes Medical Institute, University of Washington, Box 357370, Seattle, 98195, WA, USA

    Marc A. Gavin, Sally R. Clarke, Ella Negrou, Alena Gallegos & Alexander Rudensky

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Supplementary information

Web Figure 1.

Known genes showing differential expression between B6 CD4+CD25+ and CD4+CD25- cells as determined by cRNA hybridization to Affymetrix mu11K and mu19K chips. Affymetrix fold-change values were calculated with their GeneChip software so that negative and positive fold change values indicate lower and higher expression in freshly isolated B6 CD4+CD25+ versus CD4+CD25- cells, respectively. Gene annotation numbers starting with TC and ET refer to TIGR Mouse Gene Index entries (see http://www.tigr.org/tdb/mgi/). Biotinylated cRNA was generated with one (Exp. 1) or two (Exp. 2) rounds of in vitro transcription (see Mthods). (GIF 75 kb)

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Gavin, M., Clarke, S., Negrou, E. et al. Homeostasis and anergy of CD4+CD25+ suppressor T cells in vivo. Nat Immunol 3, 33–41 (2002). https://doi.org/10.1038/ni743

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