Fig. 8.22 The rearrangement of T-cell receptor γ and δ genes in the mouse proceeds in waves of cells expressing different Vγ and Vδ gene segments. At about 2 weeks of gestation in the mouse, the Cγ1 locus is expressed with its closest V gene (Vγ5). After a few days, Vγ5-bearing cells decline in numbers in the thymus (first row of panels) and are replaced by cells expressing the next most proximal gene, Vγ6. Both these rearranged γ chains are expressed with the same rearranged δ-chain gene, as shown in the lower panels, and there is little junctional diversity in either the Vγ or the Vδ chain. As a consequence, most of the γ:δ T cells produced in each of these early waves share the same specificity, although the antigen recognized in each case is not known. The Vγ5-bearing cells become established selectively in the epidermis; they are programmed to secrete keratinocyte growth factor and inflammatory cytokines and chemokines. In contrast, Vγ6-bearing cells become established in the lung, the dermis of the skin, and the epithelium of the reproductive tract, and are programmed to secrete IL-17. The next wave of γδ development begins on day 17 of gestation, and produces two different populations. One population rearranges and expresses the Vγ4 chain, which pairs with heterogeneous delta chains. These Vγ4-bearing cells are the second subset of Tγ:δ-17 (IL-17-secreting) cells, and home to lymph nodes, spleen, lung, and the dermis of the skin. The second population in this wave expresses Vγ1, and homes to lymph nodes, spleen, and liver. Some of these cells are paired with Vγ6 chains and are programmed to secrete IL-4 and IFN-γ, and represent γ:δ NKT cells. Finally, the last wave of γ:δ T-cell development begins late during fetal development, and persists into adulthood. This last wave includes a heterogeneous population of cells bearing Vγ1, Vγ2, and Vγ4 chains paired with many different delta chains. These cells home to lymphoid organs and are programmed to secrete IFN-γ. The other population in this last wave are cells bearing the Vγ7 chain paired with heterogeneous delta chains. These γ:δ cells home to the intestinal epithelium and are programmed to secrete IFN-γ as well as antimicrobial compounds. Although γ:δ T cells continue to be produced after birth, at this stage the α:β T-cell lineage becomes the dominant population developing in the thymus.
Fig. 8.23 Dendritic epidermal T cells reside within the epithelial layer, forming an interdigitating network with Langerhans cells. This face-on view of a murine epidermal sheet shows Langerhans cells (green) and dendritic epidermal T cells (dETCs; red) forming an interdigitating network within the layers of the epidermis. The epidermal epithelial cells are not visible in this fluorescence image. The branching dendritic-like form of these γ:δ T cells is the source of their name. Although the ligands for all γ:δ T-cell receptors are not known, some γ:δ T cells recognize nonclassical MHC molecules (see Sections 6-16 and 6-17), which can be induced in epithelia by stresses such as UV damage or pathogens. Thus, dETCs may serve as sentinels of such damage, producing cytokines that activate the innate immune response and, in turn, adaptive immunity. Courtesy of Adrian Hayday.
subsets of γ:δ T cells. Why certain V, D, and J gene segments are selected for rearrangement at particular times during embryonic development remains incompletely understood.