CYTOKINE PROFILE AND ULTRASTRUCTURE OF INTRAEPITHELIAL GAMMA-DELTA T-CELLS IN CHRONICALLY INFLAMED HUMAN GINGIVA SUGGEST A CYTOTOXIC EFFECTOR FUNCTION

We have shown that gamma delta T cells in human gingiva have an intrae pithelial location and, that in the chronic inflammatory disease perio dontitis, the expression of CD45RO and CD8 or CD4 is induced on gamma delta T cells. To study the role of gamma delta T cells in local antib acterial responses, we determined the cytokine profiles of isolated hu man gingival cells. Different T cell subpopulations, isolated by posit ive selection with mAb-coated magnetic beads and macrophages, as well as epithelial cells, were analyzed for expression of mRNA for 15 cytok ines by reverse transcriptase-PCR. The ultrastructure of gingival gamm a delta T cells was also studied. The gamma delta T cells expressed mR NA for lFN-gamma, TNF-alpha, TGF-beta 1, and IL-6. Expression of IFN-g amma was a consequence of inflammation. CD4(+) gamma delta T cells exp ressed IFN-gamma only, whereas CD8(+) gamma delta T cells expressed al l four cytokines. CD8(+) cells expressing IFN-gamma, TNF-alpha, and IL -6 in combination suggest a cytotoxic effector function. Gingival gamm a delta T cells contained cytoplasmic electron-dense membrane-bound gr anules and multivesicular bodies that are ultrastructural characterist ics of cytotoxic cells. Epithelial cells from inflamed gingiva express ed HLA-DR, CD1a, CD1c, and heat shock protein 60 on the cell surface. They also expressed mRNA for IL-1 beta, IL-6, IL-8, TNF-alpha, and TGF -beta 1. Thus, epithelial cells may function as accessory cells in imm une activation and, at the same time, be target cells for CD8(+) gamma delta T cells reactive with CD1 Ag or heat shock protein. These resul ts suggest that gamma delta T cells constitute a first line of defense in gingiva, preventing entrance of pathogens by cytotoxicity against infected and stressed epithelial cells, and by control of epithelial c ell growth through secretion of regulatory cytokines.