Before TCR rearrangements, T cell progenitors are committed not only to the alpha beta and gamma delta T cell lineage but also to various subsets of both lineages. In the mouse, distinct gamma delta T cell subsets can develop in the fetal thymus, the adult thymus, or independently of a thymus, probably in intestinal epithelia. The two subsets that develop in the fetal thymus home to and are maintained throughout adult life in the skin and the mucosa of the uterus, vagina, and tongue. They are monospecific. This unusual restriction in receptor repertoires is the result of severe limitations in the generation of diversity in the fetal progenitors of these subsets and the thymic selection. After birth, one gamma delta T cell subset appears in the blood, spleen, and lymph nodes and one in the intestinal epithelia. The receptor repertoires of these subsets are characterized by the preferential usage of particular V gamma gene segments and extensive junctional diversity. Several murine and human gamma delta T cell clones have been shown to recognize classical MHC class I and class II proteins or MHC class I-like proteins, and in very few cases the presented peptides are known. We suspect that the various murine gamma delta T cell subsets interact with different antigen presenting cells which utilize different antigen presenting proteins and reside in different tissues. The function of gamma delta T cells remains unknown. Preliminary results of experiments with gene knock out mice which lack either alpha beta T cells or gamma delta T cells or both suggest that gamma delta T cells do not function as helper cells in humoral immune responses but may complement alpha beta T cells in the defense against various microorganisms.

SummaryMany body surfaces harbor organ-specific γδ T cell compartments that contribute to tissue integrity. Thus, murine dendritic epidermal T cells (DETCs) uniquely expressing T cell receptor (TCR)-Vγ5 chains protect from cutaneous carcinogens. The DETC repertoire is shaped by Skint1, a butyrophilin-like (Btnl) gene expressed specifically by thymic epithelial cells and suprabasal keratinocytes. However, the generality of this mechanism has remained opaque, since neither Skint1 nor DETCs are evolutionarily conserved. Here, Btnl1 expressed by murine enterocytes is shown to shape the local TCR-Vγ7+ γδ compartment. Uninfluenced by microbial or food antigens, this activity evokes the developmental selection of TCRαβ+ repertoires. Indeed, Btnl1 and Btnl6 jointly induce TCR-dependent responses specifically in intestinal Vγ7+ cells. Likewise, human gut epithelial cells express BTNL3 and BTNL8 that jointly induce selective TCR-dependent responses of human colonic Vγ4+ cells. Hence, a conserved mechanism emerges whereby epithelia use organ-specific BTNL/Btnl genes to shape local T cell compartments.

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IL-17 production by γδ T cells is required for tumor cell infiltration by IFN-γ–producing CD8+ T cells and inhibition of tumor growth in response to anthracyclines.