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CCR6 and NK1.1 distinguish between IL-17A and IFN-gamma-producing gammadelta effector T cells

Jan D Haas1, Frano H Malinarich González, Susanne Schmitz

  • 1Hannover Medical School, Institute for Immunology, Hannover, Germany.

European Journal of Immunology
|October 16, 2009
PubMed

Insights

Two distinct gammadelta T cell lineages develop in the thymus, producing either IL-17A or IFN-gamma. CCR6+ cells make IL-17A, while NK1.1+ cells make IFN-gamma, influencing immune responses.

Area of Science:

  • Immunology
  • T cell differentiation

Background:

  • Gammadelta T cells are crucial innate immune cells producing IL-17A and IFN-gamma.
  • The differentiation pathways and signals guiding gammadelta T cell cytokine production in the thymus remain incompletely understood.

Purpose of the Study:

  • To elucidate the distinct lineages and differentiation signals of effector gammadelta T cells in the thymus.
  • To characterize the cytokine production profiles and tissue distribution of these gammadelta T cell subsets.

Main Methods:

  • Flow cytometry analysis of thymic gammadelta T cells.
  • Cytokine production assays (IL-17A, IFN-gamma) upon stimulation.
  • Assessment of cell surface marker expression (CCR6, NK1.1, CCR9).
  • Analysis of gammadelta T cell distribution in lymphoid tissues.

Main Results:

  • Thymic effector gammadelta T cells segregate into CCR6+ (IL-17A-producing) and NK1.1+ (IFN-gamma-producing) lineages.
  • NK1.1+ cells show reduced CCR9 expression and are abundant in peripheral lymphoid tissues.
  • Cytokine production is differentially regulated by IL-12, IL-18, and IL-23.
  • CCR6+ gammadelta T cells exhibit higher responsiveness to T cell receptor stimulation.

Conclusions:

  • Distinct thymic differentiation pathways generate specialized gammadelta T cell subsets for specific immune functions.
  • CCR6+ IL-17A-producing gammadelta T cells may arise from less stringent T cell receptor-dependent selection than IFN-gamma-producing NK1.1+ cells.
  • These findings provide insights into the development and functional specialization of gammadelta T cells in immunity.

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