Immunological studies of natural killer cell activity in patients with atopic dermatitis

Lesko, Michael Jan (1986) Immunological studies of natural killer cell activity in patients with atopic dermatitis. PhD thesis, University of Glasgow.

Abstract

Some patients with atopic dermatitis (AD) react abnormally to a number of cutaneous viral infections. Herpes simplex, for example can become widely disseminated with severe systemic symptoms. This susceptibility of AD patients may be due, at least in part, to deficient natural killer cell function. This study investigated the NK cell activity of AD patients using a standard four hour chromium release assay with the erythroleukaemic cell line K562 as the target cell. The NK cell activity of patients with AD was significantly reduced as compared with normal age and sex matched controls. The effect of the length of incubation time of the assay, removal of phagocytic/adherent cells and the use of target cells other than K562 on the standard four hour assay were examined. Increasing the incubation time from 4 to I8 hours and removing phagocytic/adherent cells resulted in an increase in NK cell activity, though the difference in response between patients and controls was maintained. In contrast the overall NK cell activity was reduced when target cells other then K562 were used, although the NK cell activity of the controls remained consistently higher than the patients. Atopic dermatitis is a chronic relapsing disorder and to determine whether or not NK cell activity fluctuated with disease xxiii severity NK cell activity was examined sequentially over a 12 month period in a group of patients. An inverse correlation was found between disease severity and NK cell activeity, ie. the more severe the disease the lower the NK cell activity. A strong correlation was also confirmed between clinical activity of the disease and IgE level. The reduction in NK cell activity in AD could result from either a qualitative abnormality, ie. normal numbers of effector cells with abnormal function, or a quantitative abnormality, ie. reduced numbers of effector cells. Effector cell numbers were counted using two monoclonal antibodies, HNK-1 (Leu) and Leu-11. Numbers were then correlated with function, as measTored by chromium release. Using HNK-l it appeared there was a reduction in the numbers of effector cells and this correlated v;ith the reduced activity. HNK-1 does not however, stain all NK effector cells. Using Leu-llb, which is a more specific reagent, showed normal numbers of effector cells are present in the peripheral circulation of patients as compared with controls. The reduced NK cell activity in atopic dermatitis was therefore thought to be due to a functional abnormality in the effector cell's lytic cycle. The reduction of NK cell activity could be caused by inhibitors in the serum of patients with AD. This was investigated by incubating effector cells from both AD patients, and normal controls in medium supplemented with either serum from patients with AD, normal controls or foetal calf serum (PCS). The M cell activity was estimated following either a normal four hour assay, an extended 18 hour assay or a standard four hour assay following an 18 hour preincubation in the supplemented media. Using these three protocols no significant increase was observed in the patient's effector cell activity following incubation in medium supplemented with control serum nor was there a significant decrease in control effector cell activity following incubation in medium supplemented with patients' serum. The results of this study suggest that reduced NK cell activity in AD may be related to the treatment of the disease rather than the disease itself. (Abstract shortened by ProQuest.).

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Immunology.
• Colleges/Schools: College of Medical Veterinary and Life Sciences
• Supervisor's Name: Parrott, Prof. D.M.V.
• Date of Award: 1986
• Depositing User: Enlighten Team
• Unique ID: glathesis:1986-72069
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 24 May 2019 15:11
• Last Modified: 15 Jun 2021 10:30
• URI: https://theses.gla.ac.uk/id/eprint/72069