Studies of immunological molecules in human oral keratinocytes.

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Studies of immunological molecules in human oral keratinocytes.

Dorrego, Mariana Villarroel; (2004) Studies of immunological molecules in human oral keratinocytes. Doctoral thesis (Ph.D), University College London. Green open access

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Abstract

Immunological studies in oral keratinocytes The discovery that the stratified squamous epithelium covering oral mucosa can express class II molecules of the Major Histocompatibility Complex (MHC) in pathological situations raised the possibility that oral keratinocytes are immunologically active, and might function as antigen presenting cells. For effective T lymphocyte activation, APC require, in addition to MHC II, appropriate costimulatory signals. This study investigated the expression and function of three membrane-bound costimulatory molecules, CD40, CD80 and CD86, in oral keratinocytes. Using flow cytometry, it was confirmed that oral keratinocytes "switch on" expression of MHC class II molecules after stimulation with IFNy in vitro. With one exception (of nine tested), keratinocyte lines expressed CD40 constitutively, by contrast, CD80 and CD86 were universally absent. These findings were confirmed using Western blotting. Immunohistochemical staining of oral mucosal sections localised CD40 to basal and parabasal keratinocytes, consistent with its known role in apoptosis. When keratinocytes were stimulated with soluble CD40 ligand, and two out of the three anti-CD40 antibodies tested, cell proliferation was significantly inhibited. By contrast, a third anti-CD40 antibody significantly increased proliferation. OSC-19, derived from a metastatic oral squamous cell carcinoma, was the only keratinocyte line to lack expression of CD40. Transfection of CD40 gene into this line produced increased expression of MHC class II, CD80, CD86 and ICAM-1, and a decreased proliferation rate, when compared with null transfectants and parental cells. All oral keratinocyte lines tested were capable of inducing allogeneic T lymphocyte proliferation, however, OSC19 keratinocytes required prior transfection with CD40.

Type:	Thesis (Doctoral)
Qualification:	Ph.D
Title:	Studies of immunological molecules in human oral keratinocytes.
Open access status:	An open access version is available from UCL Discovery
Language:	English
Additional information:	Thesis digitised by ProQuest
URI:	https://discovery.ucl.ac.uk/id/eprint/10101811