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COPYRIGHT 2002 Science Reviews Ltd.
Accumulative evidence suggests that resident [gamma][delta] T cells in epithelia are biologically distinct from systemic [gamma][delta] T cells in the circulation. Murine resident [gamma][delta] T cells have innate immune characteristics and play an important role in tissue homeostasis after damages. In contrast, a unique subset of circulating [gamma][delta] T cells in primates, like [alpha][beta] T cells, can mount adaptive immnune responses in infections. This article compares biological features between resident and circulating [gamma][delta]T cells.
Introduction
Two lineages of T cells can be defined by their expression of T cell receptors (TCR) [alpha][beta] or [gamma][delta] heterdimers. [gamma][delta] T cells were indeed discovered in mid-1980s based on the structural similarity between their TCR and those of [alpha][beta] T cells. (1) While the majority of T cells in the blood and lymphoid tissues are [alpha][beta] T cells, [gamma][delta] T cells account for a minor population of T cells. In adult animals and humans, [gamma][delta] T cells constitute about 1-5% of circulating lymphocytes and those in lymphoid tissues, but comprise up to 50% of T cells in epithelia or mucosae in the skin and intestine. (2) [gamma][delta] T cell population can be separated into different subsets or subpopulations based on their expression of V[gamma] or V[delta] elements. These subsets can be further divided into two major groups based on tissue distribution and TCR diversity: (1). Resident [gamma][delta] T cells with limited TCR diversity, found in skin and uterine epithelia and t hose with diverse TCR in mucosae of the organs other than the skin and uterine; (2). Circulating (systemic) [gamma][delta] T cells with great TCR diversity, found in the blood and lymphoid tissues. Although [gamma][delta] T cells resemble [alpha][beta] T cells in the process of thymic-dependent development or maturation, their antigen specificity and immune biology appear to be different from those of [alpha][beta] T cells. In fact, [gamma][delta] T cells have been considered to behave differently from [alpha][beta] T cells in host defense or immune surveillance. However, [gamma][delta] T cells still preserve some of immunological characteristics for their [alpha][beta] T cell counterparts, which include diverse TCR repertoires, TCR-mediated recognition of antigens and clonal expansions in response to infections. Recent studies have made significant progress for our understanding of immune biology of [gamma][delta] T cells. This review discusses new discoveries or concepts conceiving notable similarities and differences in biological features between resident and circulating [gamma][delta] T cells.
Resident (intraepithelial) and circulating [gamma][delta] T cells Resident [gamma][delta] T cells in epithelia are quite different in TCR repertoire and distribution from circulating systemic [gamma][delta] T cells or [alpha][beta] T cells. Large numbers of [gamma][delta] T cells do not circulate in the blood and lymphoid tissues. Instead, they are the major T cells that take up residence in the skin, (3,4) lung, (5) intestine, (6,7) uterus, vagina and tongue. (8) These [gamma][delta] T cells localize within the epithelium at the interface of the host with its environment and, therefore, contribute to the component of intraepithelial lymphocytes (IELs). Given the great surface area of epithelia, resident IEL can form a substantial fraction of T cell pools in the body. In humans and mice, TCR repertoires of [gamma][delta] IELs in different compartments display little overlap with those [gamma][delta] T cells in peripheral blood, spleen, and lymph nodes. In contrast to other [gamma][delta] IELs, [gamma][delta] TCR-bearing dendritic epidermal T cells (DETCs) found in the murin e skin and uterus are homogeneous T cell population and express invariant TCR comprised of V[gamma]3V[delta]1 or V[gamma]6V[delta]1, respectively. (8-10) In the epidermis, DETCs are concentrated as many as 500 cells per square centimeter. Through their spiny, stretched-out or finger-like contact with many other skin cells, DETCs contribute to the integrity of epithelia tissues that make up the outermost layers of skin. In humans, DETCs are hardly seen in the epidermis of skin, but can be found in the dermis. The fundamental mechanisms for the difference between these species are not known.
Immune mechanisms for shaping [gamma][delta] T cell repertoires are poorly understood. The highly restricted use of TCR by murine DETCs suggests that these cells are recruited from a wave of thymic emigrants during the early thymic ontogeny. It is also possible that the selection pressure driven from skin epithelia plays a crucial role in the formation of skin IELs. Although [gamma][delta] T cells develop in a thymic-dependent fashion, intestinal [gamma][delta] IEL can be thymic-independent cells during...
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