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

Yafei Huang, Ryan A. Heiser, Thiago O. Detanico, Andrew Getahun, Greg A. Kirchenbaum, Tamara L. Casper, M. Kemal Aydintug, Simon R. Carding, Koichi Ikuta, Hua Huang, John C. Cambier, Lawrence J. Wysock, Rebecca L. O’Brien, Willi K. Born

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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.
Original languageEnglish
Pages (from-to)E39-E48
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America (PNAS)
Volume112
Issue number1
Early online date18 Nov 2014
DOIs
Publication statusPublished - 10 Jan 2015

Keywords

  • gammadelta T cell
  • interleukin-4
  • autoimmunity
  • immunoglobulin
  • tolerance

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