γδ T cells: firefighters or fire boosters in the front lines of inflammatory responses

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Abstract
Intradermal inoculation of cloned self-reactive alphabeta T cells into the footpads of mice induced cutaneous graft-versus-host disease (GVHD), and after recovery from GVHD, the epidermis became resistant to subsequent attempts to induce GVHD. Resistance to GVHD was not induced in the epidermis of T-cell receptor delta-deficient (TCRdelta(-/-)) mice that lacked gammadelta T cells bearing canonical Vgamma5/Vdelta1(+)gammadeltaTCRs, known as dendritic epidermal T cells (DETCs), and resistance was restored by reconstitution of these mutant mice with precursors of Vgamma5(+) DETCs. Pulmonary infection by Cryptococcus neoformans induced an increase of gammadelta T cells in the lung, and in comparison with wildtype mice, TCRdelta(-/-) mice eliminated C. neoformans more rapidly and synthesized more interferon-gamma in the lung. In the mouse small intestine, the absence of gammadelta T cells is associated with a reduction in epithelial cell turnover and downregulation of the expression of major histocompatibility complex class II molecules. The protective role of gammadelta T cells was verified in a dextran sodium sulfate-induced inflammatory bowel disease (IBD) model, whereas in a spontaneous model of IBD, gammadelta T cells were involved in the exacerbation of colitis in TCRalpha(-/-) mice. Taken together, in addition to the homeostatic regulation of epithelial tissues, gammadelta T cells appear to play a pivotal role in the modification of inflammatory responses induced in many organs containing epithelia.