International Reviews of Immunology, Early Online:1–22, 2013 C Informa Healthcare USA, Inc. Copyright ISSN: 0883-0185 print / 1563-5244 online DOI: 10.3109/08830185.2013.863306
REVIEW
Int Rev Immunol Downloaded from informahealthcare.com by Technische Universiteit Eindhoven on 07/09/14 For personal use only.
Phenotypic and Functional Plasticity of Gamma–Delta (γ δ) T Cells in Inflammation and Tolerance Sourav Paul, Amit Kumar Singh, Shilpi, and Girdhari Lal National Centre for Cell Science, Pune, Maharashtra, India Gamma–delta T cells (γ δ T cells) are an unique group of lymphocytes and play an important role in bridging the gap between innate and adaptive immune systems under homeostatic condition as well as during infection and inflammation. They are predominantly localized into the mucosal and epithelial sites, but also exist in other peripheral tissues and secondary lymphoid organs. γ δ T cells can produce cytokines and chemokines to regulate the migration of other immune cells, can bring about lysis of infected or stressed cells by secreting granzymes, provide help to B cells and induce IgE production, can present antigen to conventional T cells, activate antigen presenting cells (APC) maturation, and are also known to produce growth factors that regulate the stromal cell function. γ δ T cells spontaneously produce IFN-γ and IL-17 cytokines compared to delayed differentiation of Th1 and Th17 cells. In this review, we discussed the current knowledge about the mechanism of γ δ T cell function including its mode of antigen recognition, and differentiation into various subsets of γ δ T cells. We also explored how γ δ T cells interact with different types of innate and adaptive immune cells, and how these interactions shape the immune response highlighting the plasticity and role of these cells—protective or pathogenic under inflammatory and tolerogenic conditions. Keywords autoimmunity, gamma–delta T cells, regulatory CD4 T cells, Th17 cells, tolerance
INTRODUCTION Gamma–delta (γ δ) T cells represent a minor population of T lymphocyte that uses γ - and δ- T cell receptor (TCR) gene rearrangement and express as γ δ TCR on the surface. There are several features that makes γ δ T cells distinct from conventional αβ T cells such as—(1) γ δ T cells recognize different types of antigens; (2) spontaneous production of cytokines; (3) have a different and unique function; (4) enjoy the benefit of its anatomical localization and providing the better protection; (5) play a crucial role in protection from specific pathogens. Recent evidence indicates that γ δ T cells are also present in the jawed vertebrates, and are highly conserved [1]. αβ- and γ δ- T cells both develop from a common progenitor precursor T cells in the thymus. Divergence of γ δ T cells from αβ T cells takes place at the DN3 stage during T cell development [2]. It has been proposed that separation of αβ and γ δ T cell lineage is independent of TCR signals [3, 4], whereas others demonstrated that TCR signal strength determine the lineage commitment [5, 6]. γ δ T cells represent
REVIEW
Int Rev Immunol Downloaded from informahealthcare.com by Technische Universiteit Eindhoven on 07/09/14 For personal use only.
Phenotypic and Functional Plasticity of Gamma–Delta (γ δ) T Cells in Inflammation and Tolerance Sourav Paul, Amit Kumar Singh, Shilpi, and Girdhari Lal National Centre for Cell Science, Pune, Maharashtra, India Gamma–delta T cells (γ δ T cells) are an unique group of lymphocytes and play an important role in bridging the gap between innate and adaptive immune systems under homeostatic condition as well as during infection and inflammation. They are predominantly localized into the mucosal and epithelial sites, but also exist in other peripheral tissues and secondary lymphoid organs. γ δ T cells can produce cytokines and chemokines to regulate the migration of other immune cells, can bring about lysis of infected or stressed cells by secreting granzymes, provide help to B cells and induce IgE production, can present antigen to conventional T cells, activate antigen presenting cells (APC) maturation, and are also known to produce growth factors that regulate the stromal cell function. γ δ T cells spontaneously produce IFN-γ and IL-17 cytokines compared to delayed differentiation of Th1 and Th17 cells. In this review, we discussed the current knowledge about the mechanism of γ δ T cell function including its mode of antigen recognition, and differentiation into various subsets of γ δ T cells. We also explored how γ δ T cells interact with different types of innate and adaptive immune cells, and how these interactions shape the immune response highlighting the plasticity and role of these cells—protective or pathogenic under inflammatory and tolerogenic conditions. Keywords autoimmunity, gamma–delta T cells, regulatory CD4 T cells, Th17 cells, tolerance
INTRODUCTION Gamma–delta (γ δ) T cells represent a minor population of T lymphocyte that uses γ - and δ- T cell receptor (TCR) gene rearrangement and express as γ δ TCR on the surface. There are several features that makes γ δ T cells distinct from conventional αβ T cells such as—(1) γ δ T cells recognize different types of antigens; (2) spontaneous production of cytokines; (3) have a different and unique function; (4) enjoy the benefit of its anatomical localization and providing the better protection; (5) play a crucial role in protection from specific pathogens. Recent evidence indicates that γ δ T cells are also present in the jawed vertebrates, and are highly conserved [1]. αβ- and γ δ- T cells both develop from a common progenitor precursor T cells in the thymus. Divergence of γ δ T cells from αβ T cells takes place at the DN3 stage during T cell development [2]. It has been proposed that separation of αβ and γ δ T cell lineage is independent of TCR signals [3, 4], whereas others demonstrated that TCR signal strength determine the lineage commitment [5, 6]. γ δ T cells represent
