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 intraepithelial location and, that in the chronic inflammatory disease periodontitis, 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 antibacterial responses, we determined the cytokine profiles of isolated human gingival cells. Different T cell subpopulations, isolated by positive selection with mAb-coated magnetic beads and macrophages, as well as epithelial cells, were analyzed for expression of mRNA for 15 cytokines by reverse transcriptase-PCR. The ultrastructure of gingival gamma delta T cells was also studied. The gamma delta T cells expressed mRNA for IFN-gamma, TNF-alpha, TGF-beta 1, and IL-6. Expression of IFN-gamma was a consequence of inflammation. CD4+ gamma delta T cells expressed IFN-gamma only, whereas CD8+ gamma delta T cells expressed all four cytokines. CD8+ cells expressing IFN-gamma, TNF-alpha, and IL-6 in combination suggest a cytotoxic effector function. Gingival gamma delta T cells contained cytoplasmic electron-dense membrane-bound granules and multivesicular bodies that are ultrastructural characteristics of cytotoxic cells. Epithelial cells from inflamed gingiva expressed 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 immune activation and, at the same time, be target cells for CD8+ gamma delta T cells reactive with CD1 Ag or heat shock protein. These results 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 cell growth through secretion of regulatory cytokines.
Lundqvist
C
C
Department of Immunology, University of Umeå, Sweden.
Baranov
V
V
Teglund
S
S
Hammarström
S
S
Hammarström
M L
ML
D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics; D004847:Epithelial Cells; D004848:Epithelium / Q000276:immunology; D015870:Gene Expression; D005881:Gingiva / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005891:Gingivitis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008854:Microscopy, Electron; D012333:RNA, Messenger / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure
D016207:Cytokines; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma