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

Intradermal inoculation of cloned self-reactive alpha beta 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 (TCR delta(-/-)) mice that lacked gamma delta T cells bearing canonical V gamma 5/V delta 1(+) gamma delta TCRs, known as dendritic epidermal T cells (DETCs), and resistance was restored by reconstitution of these mutant mice with precursors of V gamma 5(+) DETCs. Pulmonary infection by Cryptococcus neoformans induced an increase of gamma delta T cells in the lung, and in comparison with wildtype mice, TCR delta(-/-) mice eliminated C. neoformans more rapidly and synthesized more interferon-gamma in the lung. In the mouse small intestine, the absence of gamma delta 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 gamma delta T cells was verified in a dextran sodium sulfate-induced inflammatory bowel disease (IBD) model, whereas in a spontaneous model of IBD, gamma delta T cells were involved in the exacerbation of colitis in TCR alpha(-/-) mice. Taken together, in addition to the homeostatic regulation of epithelial tissues, gamma delta T cells appear to play a pivotal role in the modification of inflammatory responses induced in many organs containing epithelia.