How γδ T Cells Develop and Generate Immune Responses

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In the vast realm of the immune system, γδ T cells stand as a fascinating enigma. γδ T cells possess a distinct lineage and play a multifaceted role in immune responses. These unique cells have captured the attention of researchers and immunologists worldwide.

Creative Biolabs embarks on a captivating journey into the world of γδ T cells, exploring their origins, maturation, and diverse contributions to immune responses. A better understanding could aid in better γδ T cell therapy development.

Development of γδ T Cells

The genesis of γδ T cells begins within the thymus, a primary lymphoid organ that orchestrates T cell development. Within the thymic cortex, a small subset of progenitor cells commits to the γδ T cell lineage, setting the stage for their unique fate.

  • In healthy adults, γδ T cells account for 1% to 5% of peripheral blood T cells. They are mainly distributed in mucosal and subcutaneous tissues such as the intestinal tract, respiratory tract, and urogenital tract. They are one of the main components of intraepidermal lymphocytes and intraepithelial lymphocytes (IEL) in mucosal tissues.
  • γδ T cells are T cells that perform innate immune functions, and their TCR consists of γ and δ chains. γδ T cells are a type of immune cell that can not only kill cancer cells and tumor stem cells, but also recognize cancer antigens. Most γδ T cells are CD4-CD8-, that is, they do not express CD4 and CD8 molecules on their cell surface, but a few can express CD4 or CD8, which can participate in immune regulation and immune response.

This attribute makes them indispensable players in the frontline of immune surveillance against various threats, including infections and tumors.

The development of γδ T cells in the thymus. Fig. 1 The development of γδ T cells in the thymus. (Parker M E and Ciofani M, 2020)

Subsets of γδ T Cells

γδ T cells can be classified into different subsets based on the expression of specific TCR chains and cell surface markers. Two primary subsets are the Vδ1 and Vδ2 γδ T cells.

  • Vδ1 cells are prevalent in tissues like the gut and skin and play a critical role in mucosal immunity.
  • Vδ2 cells are prominent in peripheral blood and can recognize phosphorylated antigens commonly associated with microbial infections.

Understanding the differential functions of these subsets offers valuable insights into their contributions to immune responses.

γδ T Cells in Immune Responses

When the moment of truth arrives, and the immune system faces an imminent threat, γδ T cells function. Their unique ability to bridge the innate and adaptive immune responses makes them pivotal in various immune scenarios.

  • In the context of infections, γδ T cells respond rapidly to pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs), promptly initiating an innate-like immune response. Their cytokine production and cytotoxic capabilities contribute to pathogen clearance and immune regulation, orchestrating the overall immune response.
  • Furthermore, γδ T cells are not confined to their roles in infections; they also play a vital role in tumor immunosurveillance. Their ability to recognize and eliminate cancerous cells, particularly those that downregulate MHC molecules to evade αβ T cell recognition, makes them an invaluable asset in cancer immunotherapy strategies.

Creative Biolabs and other esteemed research institutions around the world are devoted to deciphering the mysteries of these unique immune cells, paving the way for innovative therapies and a deeper understanding of immune system complexity.

To learn more about the possibility of therapeutic development, please feel free to contact us.


  1. Parker M E and Ciofani M. Regulation of γδ T cell effector diversification in the thymus. Frontiers in immunology, 2020, 11: 42.
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