gamma delta T cells: Functional plasticity and heterogeneity

gamma delta T cells are a unique and highly conserved lineage of T cells. Differences in their tissue distribution and the types and mode of antigen recognition distinguish gamma delta T cells from alpha beta T cells. The potential for gamma delta T-cell antigen receptor diversity and the number of unique antigen receptors that can be generated is greater than that of alpha beta T cells and B cells combined. This potential is, however, not realized. gamma delta T cells are the first lineage of T cells to be generated; most populations are produced during fetal development. Genetic and environmental factors operate to produce or select populations of gamma delta T cells that express antigen receptors encoded by specific gene segments. Human and mouse gamma delta T-cell repertoires are characterized by cells that express antigen receptors that are encoded by a single V gamma - and V delta -gene segment Increased numbers of gamma delta T cells have been described in a variety of infectious and autoimmune diseases. In experimental animal models of inflammation, gamma delta T-cell involvement is staged; it occurs before and/or after alpha beta T-cell responses, coincident with or after the removal of the inflammatory stimulus. Functional analyses suggest that gamma delta T cells perform immunoregulatory functions that are complementary to the function of alpha beta T cells. The functions that are carried out by gamma delta T cells change as the immune response progresses; different populations of gamma delta T cells, which are defined by differences in TCR V gamma -V delta gene-segment usage, perform different functions during the early and later stages of pathogen-induced immune responses. The regulated and differential expression of gamma delta TCR co-receptors by target cells also serves to restrict and regulate gamma delta T-cell effector function. Further insights into the biological function of gamma delta T cells will be provided by defining the populations of gamma delta T cells that are involved in a particular response and the conditions under which they are normally activated.