Dermal Vγ4(+) γδ T cells possess a migratory potency to the draining lymph nodes and modulate CD8(+) T-cell activity through TNF-α production

J Invest Dermatol. 2015 Apr;135(4):1007-1015. doi: 10.1038/jid.2014.516. Epub 2014 Dec 10.

Abstract

A large number of gamma delta T cells (γδ T cells) are located within epithelial tissues including the skin. In mice, epidermal and dermal γδ T cells consist of distinct subsets and have specific roles in cutaneous immune responses. A recent study demonstrated that γδ T cells and cutaneous dendritic cells migrate from the skin to the draining lymph nodes (LNs). However, it remains unclear whether they regulate the antigen-specific immune response within the LNs. Herein, we investigated their properties and role in the LNs using the Mycobacterium bovis bacille Calmette-Guérin (BCG) infection model. In vivo cell labeling analysis revealed that most of the migratory subset comprised dermal Vγ4(+) cells. This population transmigrated from the skin to the LNs in a Gi-coupled chemokine receptor-independent manner. By depleting Vγ4(+) cells, the intranodal expansion of CD8(+) T cell against BCG was significantly attenuated. In addition, in vitro analysis revealed that Vγ4(+) cells produced TNF-α and enhanced IL-12 production by dendritic cells. Taken together, these findings suggest that dermal Vγ4(+) cells are a unique subset that possesses a migratory potency to the skin-draining LNs and enhances the dendritic cell function therein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology*
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation
  • Interferon-gamma / metabolism
  • Interleukin-12 / metabolism
  • Langerhans Cells / cytology
  • Langerhans Cells / metabolism
  • Light
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mycobacterium bovis / metabolism
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Skin / immunology
  • T-Lymphocyte Subsets / immunology
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Receptors, Antigen, T-Cell, gamma-delta
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Interferon-gamma