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Updated: Apr 17, 2026
Expansion of Human Peripheral Blood γδ T Cells using Zoledronate
Published on: September 9, 2011
Five Layers of Receptor Signaling in γδ T-Cell Differentiation and Activation
Sérgio T Ribeiro1, Julie C Ribot1, Bruno Silva-Santos1
1Faculdade de Medicina, Instituto de Medicina Molecular, Universidade de Lisboa , Lisboa , Portugal.
Abstract:
The contributions of γδ T-cells to immunity to infection or tumors critically depend on their activation and differentiation into effectors capable of secreting cytokines and killing infected or transformed cells. These processes are molecularly controlled by surface receptors that capture key extracellular cues and convey downstream intracellular signals that regulate γδ T-cell physiology. The understanding of how environmental signals are integrated by γδ T-cells is critical for their manipulation in clinical settings. Here, we discuss how different classes of surface receptors impact on human and murine γδ T-cell differentiation, activation, and expansion. In particular, we review the role of five receptor types: the T-cell receptor (TCR), costimulatory receptors, cytokine receptors, NK receptors, and inhibitory receptors. Some of the key players are the costimulatory receptors CD27 and CD28, which differentially impact on pro-inflammatory subsets of γδ T-cells; the cytokine receptors IL-2R, IL-7R, and IL-15R, which drive functional differentiation and expansion of γδ T-cells; the NK receptor NKG2D and its contribution to γδ T-cell cytotoxicity; and the inhibitory receptors PD-1 and BTLA that control γδ T-cell homeostasis. We discuss these and other receptors in the context of a five-step model of receptor signaling in γδ T-cell differentiation and activation, and discuss its implications for the manipulation of γδ T-cells in immunotherapy.
Insights
Gamma delta (γδ) T-cells are crucial for immunity, with their function governed by surface receptors. Understanding these receptors is key to harnessing γδ T-cells for immunotherapy.
Area of Science:
- Immunology
- Cellular Biology
- Molecular Biology
Background:
- Gamma delta (γδ) T-cells play a vital role in immune responses against infections and tumors.
- Their effector functions, including cytokine secretion and cell killing, depend on activation and differentiation.
- Surface receptors are critical for integrating environmental signals and regulating γδ T-cell physiology.
Purpose of the Study:
- To review the impact of different surface receptor classes on human and murine γδ T-cell differentiation, activation, and expansion.
- To discuss the roles of specific receptors, including TCR, costimulatory, cytokine, NK, and inhibitory receptors.
- To explore the implications of receptor signaling for manipulating γδ T-cells in immunotherapy.
Main Methods:
- Review of existing literature on γδ T-cell surface receptors.
- Analysis of the roles of specific receptors such as CD27, CD28, IL-2R, IL-7R, IL-15R, NKG2D, PD-1, and BTLA.
- Discussion of a five-step model of receptor signaling in γδ T-cell activation and differentiation.
Main Results:
- Costimulatory receptors (CD27, CD28) differentially affect pro-inflammatory γδ T-cell subsets.
- Cytokine receptors (IL-2R, IL-7R, IL-15R) are essential for γδ T-cell functional differentiation and expansion.
- NK receptor NKG2D enhances γδ T-cell cytotoxicity, while inhibitory receptors (PD-1, BTLA) regulate homeostasis.
Conclusions:
- Surface receptors are critical regulators of γδ T-cell activation, differentiation, and function.
- Understanding receptor signaling provides a framework for manipulating γδ T-cells in therapeutic strategies.
- Targeting these receptors holds promise for advancing immunotherapy for cancer and infectious diseases.
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