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World Allergy Organization
WAO's mission: To be a global resource and advocate in the field of allergy, advancing excellence in clinical care through education, research and training as a world-wide alliance of allergy and clinical immunology societies.

World Allergy Forum: Ocular Allergy

Cells and Mediators Involved in Ocular Allergy

VL Calder

"Ocular allergy" describes a group of clinically distinct allergic eye disorders ranging from the milder disorders of seasonal and perennial allergic conjunctivitis (SAC, PAC), to the severe, and potentially sight-threatening diseases, vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC (1)). The cells and mediators involved in ocular allergy will be discussed, with particular emphasis on the more chronic diseases.

Cells in ocular allergy
In SAC and PAC, the immune response closely resembles a type I hypersensitivity, with a predominance of mast cells and eosinophils infiltrating the conjunctiva. There is no evidence for T cells playing an important role in SAC. SAC is likely to be mast cell-driven and can be successfully treated with anti-histamines and mast cell stabilisers. Treatment is less successful for PAC and very little is known about the cell types involved. SAC and PAC have different sensitising allergens, with tree, grass or weed pollen being involved in SAC, whereas PAC is thought to involve increased sensitivity to cat and house dust mite.

Giant papillary conjunctivitis (GPC), which is mainly associated with wearing contact lenses, VKC and AKC are all chronic forms of ocular allergy. However the cornea is only affected in VKC and AKC. Interestingly in all three forms of disease, there are infiltrating T cells, eosinophils, mast cells, basophils, activated macrophages, dendritic cells, some neutrophils and fibroblasts present within the conjunctival substantia propria. There is an increased expression of HLA-DR, CD3 (a pan-T cell marker) and CD1a (Langerhans’ cells). The majority of CD3+T cells are CD4+ and CD45Ro+ (memory) and increased CD25 expression was also detected, indicating the T cells were activated.(2)

Cytokines in ocular allergy
The cytokines expressed within the conjunctiva in GPC, VKC and AKC were investigated by in situ hybridisation. In all three forms of conjunctivitis, IL-3, IL-4 and IL-5 cytokines were expressed. However, both IL-2 and IFN-γ expression were significantly increased in AKC in comparison with VKC and GPC (2). This suggested that in the more severe form of allergic eye disease, there was a change towards a Th1-like cytokine profile. T cells cloned from VKC biopsies were Th2-like.(3) Comparing conjunctival T cell lines established from different forms of disease, it was found that in GPC only low levels of cytokines were produced whereas in VKC there were increases in IL-5 and IL-13 production, in agreement with a Th2-type profile. For AKC T cell lines, increases in IL-5, IL-13, IL-10 and IFN-γ were observed, suggesting that in this form of conjunctivitis, a switch of the T cell cytokine profiles was occurring.(4)

Other cell types including fibroblasts, epithelial cells, eosinophils (5) and mast cells (6) are likely to play important roles due to their ability to express costimulatory molecules and to produce cytokines and chemokines themselves.

Conclusion

Despite similar cells infiltrating the conjunctiva in chronic allergic eye disease, there are different cells and cytokines in each form of ocular allergy and further research is required to dissect out the roles for each of these.

References

  1. Bielory L. (2000) Allergic and immunologic disorders of the eye. Part II: Ocular allergy. J Allergy Clin Immunol 106: 1019-32.

  2. Metz DP, Hingorani M, Calder VL, Buckley RJ & Lightman SL (1997) T cell cytokines in chronic allergic eye disease. J Allergy Clin Immunol 100, 817-24.

  3. Maggi E, Biswas P, Del Prete G, Parronchi P, Macchia D, Simonella et al (1991) Accumulation of Th2-like helper T cells in the conjunctiva of patients with vernal conjunctivitis. J Immunol 146, 1169-74.

  4. Calder VL, Jolly G, Hingorani M, Adamson P, Leonardi A, Secchi A, Buckley RJ & Lightman S. (1999) Cytokine production and mRNA expression by conjunctival T cell lines in chronic allergic eye disease. Clin Exp Allergy 29, 1214-22.

  5. Woerly G, Roger N, Loiseau S, Dombrowicz D, Capron A, Capron M. (1999) Expression of CD28 and CD86 by human eosinophils and role in the secretion of type 1 cytokines (interleukin 2 and interferon gamma): inhibition by IgA complexes. J Exp Med 190, 487-95.

  6. Anderson DF, Zhang S, Bradding P, McGill JI, Holgate ST, Roche WR. (2001) The relative contribution of mast cell subsets to conjunctival t(h)2-like cytokines. Invest Ophthalmol Vis Sci 42, 995-1001.

 

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