γδ T cells affect IL-4 production and B-cell tolerance

Huang, Yafei, Heiser, Ryan A., Detanico, Thiago O., Getahun, Andrew, Kirchenbaum, Greg A., Casper, Tamara L., Aydintug, M. Kemal, Carding, Simon R., Ikuta, Koichi, Huang, Hua, Cambier, John C., Wysock, Lawrence J., O’Brien, Rebecca L. and Born, Willi K. (2015) γδ T cells affect IL-4 production and B-cell tolerance. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 112 (1). E39-E48.

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Abstract

γδ T cells can influence specific antibody responses. Here, we report that mice deficient in individual γδ T-cell subsets have altered levels of serum antibodies, including all major subclasses, sometimes regardless of the presence of αβ T cells. One strain with a partial γδ deficiency that increases IgE antibodies also displayed increases in IL-4–producing T cells (both residual γδ T cells and αβ T cells) and in systemic IL-4 levels. Its B cells expressed IL-4–regulated inhibitory receptors (CD5, CD22, and CD32) at diminished levels, whereas IL-4–inducible IL-4 receptor α and MHCII were increased. They also showed signs of activation and spontaneously formed germinal centers. These mice displayed IgE-dependent features found in hyper-IgE syndrome and developed antichromatin, antinuclear, and anticytoplasmic autoantibodies. In contrast, mice deficient in all γδ T cells had nearly unchanged Ig levels and did not develop autoantibodies. Removing IL-4 abrogated the increases in IgE, antichromatin antibodies, and autoantibodies in the partially γδ-deficient mice. Our data suggest that γδ T cells, controlled by their own cross-talk, affect IL-4 production, B-cell activation, and B-cell tolerance.

Item Type: Article
Uncontrolled Keywords: gammadelta t cell,interleukin-4,autoimmunity,immunoglobulin,tolerance
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 01 Apr 2016 10:20
Last Modified: 28 Oct 2019 11:37
URI: https://ueaeprints.uea.ac.uk/id/eprint/58063
DOI: 10.1073/pnas.1415107111

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