Immunobiology of delta/gamma cells
...er-like shape that contacts as many skin cells as possible. Gamma/delta T cell has two extracellular domains. The amino-terminal domain is highly variable and it’s called Variable ((Vg or VD) domain. The domain closest to the membrane is the Constant (Cg or Cd) domain. The variable domain provides the specificity with the foreign antigens and the constant domains provide the effectors functions (Barclay 1999). The constant region is responsible for sending an activation signal. Tyrosine-phosphorylation is usually the initial signal. Gamma/delta T cell has also another two gene segment which are short J (joining) genes and for the heavy chain delta there are also D (diversity) genes. Four gene segments; variable, diversity, joining and constant are rearranged during T-cell differentiation to produce a functional product (Goldsby 2001). The V domain of each chain has three complementarity determining regions (CDRs). Allison ET all (2002) noted that the complementarity-determining regions (CDRs) of the V domains exhibit a suitable binding site for phosphorylated antigens that may account for the broad antigen reactivity of peripheral blood gamma/delta T cells. There is junctional "flexibility" between the segments. Proximal to the membrane, each TCR chain has a short connecting sequence with a cysteine residue that forms a disulfide bond between both chains. It also has a transmembrane domain with positively charged amino acids that allow them to interact with chains of the signal transduction CD3 complex. ORGANIZATION OF GAMMA/DELTA T CELL GENE: Genes encoding gamma-delta heterodimer is only expressed in the T-cell lineage. Gamma chain is produced by rearrangements of V and J segments whereas delta chain is produced by rearrangements of V, D, and J segments. The gene segments for TCR chains are encoded in different chromosomes, except the delta-chain gene segments that are between the V and J gene segments of the alfa chain. This location of delta-chain gene segments has significance: a productive rearrangement of alfa-chain gene segments deletes C genes of the delta-chain, so that in a given cell the alfa-beta heterodimer cannot be co-expressed with the gamma-delta receptor. The gamma chain gene segments are clustered on chromosome 7 and the delta chain gene segments are clustered on chromosome 14. DEVELOPMENT AND MATURATION OF GAMMA/DELTA T CELL (see also fig: 1) Fig 1: Development of gamma/delta T cell Progenitors of humanT cells are derived from the bone marrow which migrates from the bone marrow via the blood stream, to the outer cortex of the thymus where they begin the thymic phase of T cell differentiation in the 8th or 9th week of development. Developing T cells in the thymus are called thymocytes. They are attracted to the thymus by a chemotactic factor secreted by thymic epithelial cells. Once in the thymus the pro-T cells express Thy-1 on their surface. At the beginning of the maturation process in the thymus, thymocytes do not express any of the characteristic molecules that T cells express. At this early stage, thymocytes are called double negative (DN) cells. The first membrane molecule to appear is c-Kit, a receptor for stem-cell growth factor. Then CD44, a cell adhesion molecule, and finally, CD25. In this stage, thymocytes proliferate but they have not rearranged their TCR genes yet. Then, thymocytes stop to expressing c-Kit, reduce the expression of CD44, and start to rearrange the TCR genes. Those thymocytes that productively rearrange gamma and delta gene segments develop into double –negative CD+gamma/delta T cell. These cells form more than 80% of CD3+ cells in early gestation and then decline in numbers to reach less than 5% in adults. The gene families encoding the gamma and delta chains are located on several chromosomes and comprise V (D) J and C gene segments. V (D) J recombination is mediated by RAG-1 and RAG-2. Gamma/delta T-cell receptors may be specialized to bind certain kinds of ligands, including heat-shock proteins and nonpeptide ligands such as mycobacterial lipid antigens. They may bind the free antigen, and/or they may bind to peptides or other antigens presented by nonclassical MHC-like molecules. DISTRIBUTION OF GAMMA/DELTA T CELL: Less than 5% of peripheral T cells have gamma/delta TCRs but they are the major type of T cells in skin, intestinal epithelium, pulmonary epithelium and lining epithelium of vagina, uterus and tongue. Gamma/delta T cells are distributed in two populations. One population, the intraepidermal lymphocytes, is found in the skin and is CD4- 8- (double-negative). The other population, the intraepithelial lymphocytes, is found in the intestinal epithelium and is CD8+.They encounter antigens on the surface of the epithelial cells that surround them rather than relying on the APCs found in lymph nodes. They are also present in very low numbers in peripheral blood and but do not recirculate between blood and lymphnodes. FUNCTIONS OF GAMMA/DELTA T CELL: Gamma delta cells can perform a vast array of immune effector functions and appear to play important roles in antimicrobial immunity as well as in chronic inflammatory reactions (Salerno et all 1998). The role of gamma/delta T cell is discussed below: Protection of epithelial cell surfaces is the main function of gamma/delta T cells. As they are situated at the interfaces between the external and internal worlds, they may represent a first line of defense against invading pathogens. Their response does seem to be quicker than that of alfa/ beta T cells. Gamma/delta T cells respond are found to many of an...