Metz, Daniela Patricia; (1994) T cells in atopic eye disease. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Background: Chronic allergic eye diseases comprise a clinically heterogeneous group of disorders, including atopic blepharoconjunctivitis (ABC), giant papillary conjunctivitis (GPC), vernal keratoconjunctivitis and atopic keratoconjunctivitis (AKC). The latter two are the most serious conditions by far, since both can be accompanied by corneal inflammation and represent potentially blinding disorders. Treatment with conventional mast cell stabilisers is often unsatisfactory and therapy therefore frequently relies on topical corticosteroids. Although a cell mediated immune response is thought to be involved in these diseases, very little is known about the cellular interactions leading to the immunopathology. T cells have been subdivided on the basis of their lymphokine production profile in the murine system. Recent evidence suggests the existence of such T cell subsets in the human system. T lymphocytes producing Interleukin (IL-) 4 and IL- 5 but no or little IL-2 and IFNy are thought to play an important regulatory role in the immunopathology of other chronic allergic conditions, such as asthma, atopic dermatitis and eczema. Aim: This study was undertaken to investigate the general cellular infiltrate in clinically distinct chronic allergic eye diseases and in particular, to study the distribution of T cell infiltrates and their activation status in order to establish their possible involvement in the regulation of immune processes in chronic allergic eye disease. Methods: Phenotypic differences and similarities of leukocytes infiltrating the different groups of chronic allergic eye disease were investigated employing immunohistochemical staining techniques. Furthermore, the production of lymphokines by T cells was analyzed utilising in situ hybridisation histochemical techniques. The in situ analysis of lymphokine mRNA expression by these T cells was carried out using 35S-labelled riboprobes for IL-2, IL-3, IL-4 and IL-5. Results: Immunohistochemistry revealed a highly significant increase in the number of CD4 + memory (CD45-RO +) T cells in tarsal conjunctival biopsies obtained from patients with VKC and GPC (p<0.001) and a significant increase in tarsal biopsies obtained from patients with AKC (p<0.01). T cells were activated, expressing HLA-DR on their surface. In addition, macrophages and Langerhans cells were upregulated significantly in the conjunctiva of patients with VKC and GPC indicating their possible role in the presentation of antigen to T cells. In situ hybridisation histochemistry revealed a significantly greater number of biopsies from patients with VKC and GPC with signal for IL-3, IL-4 IL-5 and IL-4 mRNA respectively in T cell rich areas of tarsal conjunctiva than normal controls. Although lymphokine mRNA expression was not greater in AKC than normal conjunctiva, several tarsal biopsies from patients with AKC showed mRNA expression for all lymphokines studied. Conclusions: The prevalence of large numbers of CD4+ memory T cells in VKC, GPC and AKC suggested their active involvement in the regulation of the immune response in these chronic allergic eye conditions. Although CD4+ T cells were increased in all allergic patient groups, in situ hybridisation histochemistry revealed differences in lymphokine mRNA expression by T cells infiltrating AKC and VKC. T cells infiltrating VKC bore similarities to murine Th2, while T cells present in AKC revealed a broader spectrum of lymphokine mRNA expression. Therefore, it was put forward that patients with AKC and ABC may have contained T cell populations with a deregulated lymphokine production that led to an overexpression of IL-4 and IL-5 mRNA, while T cells present in VKC and GPC represented possibly normal, late memory T cells producing lymphokines similar to murine Th2.

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