Lymphocytes: Gamma Delta Julie Gertner, INSERM, Toulouse, France Emmanuel Scotet, INSERM, Nantes, France Mary Poupot, INSERM, Toulouse, France Marc Bonneville, INSERM, Nantes, France Jean-Jacques Fournie ´, INSERM, Toulouse, France Based in part on the previous version of this Encyclopedia of Life Sciences (ELS) article, Lymphocytes: Gamma Delta by Marc Bonneville and Jean-Jacques Fournie ´. gd Lymphocytes are a subset of T lymphocytes that express the gd receptor for antigens. They are distinct from ab T lymphocytes not only by their different mode of antigen recognition but also for the functions they fulfil. These HLA-unrestricted lymphocytes are particularly attractive for developing anticancer therapies based on new activatory drugs. Introduction Antigen recognition by B and T lymphocytes is achieved by highly diverse heterodimeric receptors, the B- and T-cell receptors (TCRs). T lymphocytes can be subdi- vided into two mutually exclusive subpopulations carry- ing TCR chains encoded by either a and b or g and d gene loci. These T-cell subsets are classically referred to as ‘ab’ and ‘gd’ T cells, respectively. Like other antigen receptors, the extensive structural diversity of gd TCR is generated through somatic recombination of gene seg- ments termed variable (V), diversity (D) and joining (J). Moreover, in common with ab TCR, gd TCR is non- covalently linked to a transduction complex composed of several CD3 subunits, which triggers intracellular sig- nalling cascades and subsequent activation of T-cell effector functions following antigen recognition. See also: B Lymphocytes: Receptors; Immunoglobulin Gene Rearrangements; T-cell Receptors gd T cells, which were fortuitously discovered in humans and rodents about a decade ago, are produced by all ver- tebrates studied thus far. While they generally represent a small fraction of T cells in primary and secondary lymph- oid organs, they are greatly enriched in mucosal tissues, where they can make up the vast majority of T cells. Despite this, whether gd T cells fulfil functions distinct from, or redundant to, those achieved by ab T cells has long re- mained an enigma. Although this issue is not yet solved, several observations detailed hereafter suggest that gd T cells recognize a specific set of conserved antigens and play unique important roles in various immune responses and cell homeostatic processes. See also: Lymphoid System; Mucosal Lymphoid Tissues Distribution, Morphology and Phenotype Distribution The relative abundance of T cells bearing gd TCR varies greatly from species to species or from one body site to another. Furthermore, the individual’s age and immuno- logical history (e.g. infectious episodes) are two other im- portant parameters that critically affect the frequency of gd T cells in a given tissue location. In healthy individuals, gd T cells represent an average between 1 and 5% of peripheral blood T cells in humans, and at most 3% of spleen and lymph node T cells in rodents. Their frequency in these body sites is much higher in ruminants and birds, where they constitute up to one-third of total T cells. The fraction of T cells expressing gd TCR is greatly increased in epithe- lial sites directly contacting the external milieu. This en- richment is particularly pronounced in rodents, in which gd T cells represent at least one-third of intraepithelial T cells throughout the digestive tract and in reproductive organ mucosa, and constitute most, if not all, intraepidermal T cells. An increased frequency of gd T cells within intraep- ithelial lymphocytes of the digestive tract is also observed in humans and chickens, but their proportion in other epi- thelial sites remains a subject of debate. See also: Lymph Nodes; Spleen Morphology In peripheral blood, spleen or lymph nodes, mature gd T lymphocytes are not distinguishable from either B or other (ab) T lymphocytes by traditional Article Contents Advanced article . Introduction . Distribution, Morphology and Phenotype . TCR Structure and Recognition Repertoire . Ontogeny . Antigen Recognition . Conclusion doi: 10.1002/9780470015902.a0001195.pub2 ENCYCLOPEDIA OF LIFE SCIENCES & 2007, John Wiley & Sons, Ltd. www.els.net 1