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ARTICLE |

Distribution of Lymphocytes and Cell Adhesion Molecules in Iris Biopsy Specimens From Patients With Uveitis FREE

Denis Wakefield, MD; Peter McCluskey, MBBS; Patricia Palladinetti
[+] Author Affiliations

Accepted for publication July 31, 1991.

Reprint requests to Laboratory of Ocular Immunology, School of Pathology, University of New South Wales, PO Box 1, Kensington, New South Wales, Australia (Dr Wakefield).


Arch Ophthalmol. 1992;110(1):121-125. doi:10.1001/archopht.1992.01080130123040
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• To investigate the mechanisms responsible for lymphocyte accumulation in the eye in uveitis, we examined iris biopsy specimens that were obtained from 10 patients with uveitis and from 12 patients with cataract for the presence of adhesion molecules on vascular endothelium, uveal cells, and infiltrating inflammatory cells. Immunoperoxidase staining of iris biopsy specimens that were obtained from patients with uveitis revealed an increased expression of intercellular adhesion molecule 1 (CD54) on endothelial cells, lymphocytes, fibroblasts, and iris epithelial cells. Seven of the 10 iris biopsy specimens that were obtained from patients with uveitis had a significant inflammatory cell infiltrate. Lymphocytes (CD2 positive) that infiltrated the iris were predominantly helper T cells (70%) and strongly expressed the lymphocyte function—associated antigen 1 (CD11a, CD18) molecule, the ligand for intercellular adhesion molecule 1, in four of the seven biopsy specimens. In contrast, small numbers of lymphocytes were evident in only three (25%) of the iris biopsy specimens that were obtained from patients with cataract. Vascular endothelium from the latter group did not express intercellular adhesion molecule 1 or endothelial leukocyte adhesion molecule 1. The results of this study revealed the enhanced expression of vascular endothelial cell and lymphocyte adhesion molecules in the iris biopsy specimens that were obtained from patients with uveitis. The presence of these receptors and their presumed ligands may have important implications for the role of these molecules in the pathogenesis of uveitis.

REFERENCES

Jakobiec FA, Marboe CC, Knowles DM, et al.  Human sympathetic ophthalmia: an analysis of the inflammatory infiltrate by hybridoma monoclonal antibodies, immunochemistry, and correlation electron microscopy . Ophthalmology . 1983;;90:76-82.
Wong VG, Hersh EM, McMaster PRB.  Treatment of a presumed case of presumed sympathetic ophthalmia with methotrexate . Arch Ophthalmol . 1966;;76:66-71.
Kaplan HJ, Waldrep JC, Chan WC, Nicholson JKA, Wright JD.  Human sympathetic ophthalmia: immunologic analysis of the vitreous and uvea . Arch Ophthalmol . 1986;;104:240-245.
Chan CC, Nussenblatt RB, Fujikawa LS, et al.  Sympathetic ophthalmia: immunopathological findings . Ophthalmology . 1986;;93:690-695.
Kaplan HJ, Waldrep C, Nicholson JKA, Gordon D.  Immunological analysis of intraocular mononuclear cell infiltrate in uveitis . Arch Ophthalmol . 1984;;102:572-575.
Deschenes J, Freeman WR, Char DR, Garovoy MR.  Lymphocyte subpopulations in uveitis . Arch Ophthalmol . 1986;;104:233-236.
Chan CC, Mochizuki M, Nussenblatt RB, et al.  T lymphocyte subsets in experimental uveitis . Clin Immunol Immunopathol . 1985;;35:103-108.
Stevens G Jr, Chan CC, Wetzig RP, Nussenblatt RB, Palestine AG.  Iris lymphocytic infiltration in patients with clinically quiescent uveitis . Am J Ophthalmol . 1987;;104:508-512.
Ni M, Chan C-C, Nussenblatt RB, Li S, Mao W.  Iris inflammatory cells, fibronectin, fibrinogen and imunoglobulin in various ocular diseases . Arch Ophthalmol . 1988;;106:392-395.
Patarroyo M, Mabegoba MW.  Leukocyte adhesion to cells . Scand J Immunol . 1989;;30:129-164.
Haynes BF, Hale LP, Denning SM, Le PT, Singer KH.  The role of leukocyte adhesion molecules in cellular interactions: implications for the pathogenesis of inflammatory synovitis . Springer Semin Immunopathol . 1989;;11:163.
Masuyama J, Minato N, Kano S.  Mechanisms of lymphocyte adhesion to human vascular endothelial cells in culture . J Clin Invest . 1986;;77:1596-1601.
Gregory CD, Murray RJ, Edwards CF, Rickinson AB.  Down regulation of cell adhesion molecules LFA-3 and ICAM-1 in Epstein-Barr virus-positive Burkitt's lymphoma underlies tumour cell escape from virus-specific T cell surveillance . J Exp Med . 1988;;167:1811-1817.
Bevilacqua MP, Pober JS, Mendrick DL, Cotran RS, Gimbrone MA.  Identification of an inducible endothelial-leukocyte adhesion molecule . Proc Natl Acad Sci U S A . 1987;;84:9238-9240.
Kurzinger K, Reynolds T, Germain RN, Davignon D, Martz E, Springer TA.  A novel lymphocyte function associated antigen (LFA-1): cellular distribution, quantitative expression, and structure . J Immunol . 1981;;127:596-602.
Potarroya M, Mabegoba MW.  Leucocyte adhesion to cells in immune and inflammatory responses . Lancet . 1989;;11:1139-1142.
Dustin ML, Singer KH, Tuck DT, Springer TA.  Adhesion of T lymphoblasts to epidermal keratinocytes is regulated by interferon-gamma and is mediated by intercellular adhesion molecule-1 . J Exp Med . 1986;;167:1323-1327.
Pober JS, Gimbrone MA Jr, Lapierre LA, et al.  Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon . J Immunol . 1986;;137:1893-1896.
Wakefield D, Dunlop I, McCluskey P, Penny R.  Uveitis: aetiology and disease associations in an Australian population . Aust N Z J Ophthalmol . 1986;;14:181-186.
Hogan MJ, Kimura SJ, Thygeson P.  Signs and symptoms of uveitis . Arch Ophthalmol . 1959;;47:155-170.
Nussenblatt RB, Palestine AG, Chan CC, Roberge F.  Standardization of vitreal inflammatory activity in intermediate and posterior uveitis . Ophthalmology . 1985;;92:467-471.
Boyd AW, Wawrybe SO, Burns GF, Fecondo JV.  Intercellular adhesion molecule-1 (ICAM-1) has a central role in cell-cell contact mediated immune mechanisms . Proc Natl Acad Sci U S A . 1988;;85:3095-3099.
Bevilacqua MP, Stengelin S, Gimbrone MA, Seed B.  Endothelial leukocyte adhesion molecule-1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins . Science . 1989;;243:1160-1165.
Abi Hanna D, McCluskey P, Wakefield D.  HLA antigens in the iris and aqueous humor gamma interferon levels in anterior uveitis . Invest Ophthalmol Vis Sci . 1989;;30:990-995.
Deschenes J, Char DH, Freeman W, Nozik R, Garovoy M.  Uveitis: lymphocyte subpopulation studies . Eye . 1986;;105:246-249.
Deschenes J, Char DH, Kaleta S.  Activated T lymphocytes in uveitis . Br J Ophthalmol . 1988;;72:83-87.
Albelda SA, Buck CA.  Integrins and other cell adhesion molecules . FASEB J . 1990;;4:2868-2880.
Wuthrich RP, Jevnikar AM, Takei R, Lincher LH, Kelly VE.  Intercellular adhesion molecule-1 (ICAM-1) expression is upregulated in autoimmune murine lupus nephritis . Am J Pathol . 1990;;136:2-6.
Dustin ML, Rothlein R, Bhan AK, Dinarello CA, Springer TA.  Induction by IL-1 and interferon-gamma, tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1) . J Immunol . 1986;;137:245-254.
Mantovani A, Dejana E.  Cytokines as communication signals between leukocytes and endothelial cells . Immunol Today . 1989;;11:370-372.
Springer TA, Dustin ML, Kishimoto TK, Marlin S.  The lymphocyte function associated antigen LFA-1, CD2, and LFA-3 molecules: cell adhesion receptors of the immune system . Annu Rev Immunol . 1987;;5:223-252.
Bevilacqua MP, Pober JS, Mendrick DL, Cotran RS, Gimbrone MA.  Identification of an inducible endothelial leukocyte adhesion molecule . Proc Natl Acad Sci U S A . 1987;;84:9238-9242.
Osborn L.  Leukocyte adhesion to endothelium in inflammation . Cell . 1990;;62:3-6.
Doyle C, Strominger JL.  Interaction between CD4 and class II MHC molecules mediated cell adhesion . Nature . 1987;;330:256-259.

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Jakobiec FA, Marboe CC, Knowles DM, et al.  Human sympathetic ophthalmia: an analysis of the inflammatory infiltrate by hybridoma monoclonal antibodies, immunochemistry, and correlation electron microscopy . Ophthalmology . 1983;;90:76-82.
Wong VG, Hersh EM, McMaster PRB.  Treatment of a presumed case of presumed sympathetic ophthalmia with methotrexate . Arch Ophthalmol . 1966;;76:66-71.
Kaplan HJ, Waldrep JC, Chan WC, Nicholson JKA, Wright JD.  Human sympathetic ophthalmia: immunologic analysis of the vitreous and uvea . Arch Ophthalmol . 1986;;104:240-245.
Chan CC, Nussenblatt RB, Fujikawa LS, et al.  Sympathetic ophthalmia: immunopathological findings . Ophthalmology . 1986;;93:690-695.
Kaplan HJ, Waldrep C, Nicholson JKA, Gordon D.  Immunological analysis of intraocular mononuclear cell infiltrate in uveitis . Arch Ophthalmol . 1984;;102:572-575.
Deschenes J, Freeman WR, Char DR, Garovoy MR.  Lymphocyte subpopulations in uveitis . Arch Ophthalmol . 1986;;104:233-236.
Chan CC, Mochizuki M, Nussenblatt RB, et al.  T lymphocyte subsets in experimental uveitis . Clin Immunol Immunopathol . 1985;;35:103-108.
Stevens G Jr, Chan CC, Wetzig RP, Nussenblatt RB, Palestine AG.  Iris lymphocytic infiltration in patients with clinically quiescent uveitis . Am J Ophthalmol . 1987;;104:508-512.
Ni M, Chan C-C, Nussenblatt RB, Li S, Mao W.  Iris inflammatory cells, fibronectin, fibrinogen and imunoglobulin in various ocular diseases . Arch Ophthalmol . 1988;;106:392-395.
Patarroyo M, Mabegoba MW.  Leukocyte adhesion to cells . Scand J Immunol . 1989;;30:129-164.
Haynes BF, Hale LP, Denning SM, Le PT, Singer KH.  The role of leukocyte adhesion molecules in cellular interactions: implications for the pathogenesis of inflammatory synovitis . Springer Semin Immunopathol . 1989;;11:163.
Masuyama J, Minato N, Kano S.  Mechanisms of lymphocyte adhesion to human vascular endothelial cells in culture . J Clin Invest . 1986;;77:1596-1601.
Gregory CD, Murray RJ, Edwards CF, Rickinson AB.  Down regulation of cell adhesion molecules LFA-3 and ICAM-1 in Epstein-Barr virus-positive Burkitt's lymphoma underlies tumour cell escape from virus-specific T cell surveillance . J Exp Med . 1988;;167:1811-1817.
Bevilacqua MP, Pober JS, Mendrick DL, Cotran RS, Gimbrone MA.  Identification of an inducible endothelial-leukocyte adhesion molecule . Proc Natl Acad Sci U S A . 1987;;84:9238-9240.
Kurzinger K, Reynolds T, Germain RN, Davignon D, Martz E, Springer TA.  A novel lymphocyte function associated antigen (LFA-1): cellular distribution, quantitative expression, and structure . J Immunol . 1981;;127:596-602.
Potarroya M, Mabegoba MW.  Leucocyte adhesion to cells in immune and inflammatory responses . Lancet . 1989;;11:1139-1142.
Dustin ML, Singer KH, Tuck DT, Springer TA.  Adhesion of T lymphoblasts to epidermal keratinocytes is regulated by interferon-gamma and is mediated by intercellular adhesion molecule-1 . J Exp Med . 1986;;167:1323-1327.
Pober JS, Gimbrone MA Jr, Lapierre LA, et al.  Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon . J Immunol . 1986;;137:1893-1896.
Wakefield D, Dunlop I, McCluskey P, Penny R.  Uveitis: aetiology and disease associations in an Australian population . Aust N Z J Ophthalmol . 1986;;14:181-186.
Hogan MJ, Kimura SJ, Thygeson P.  Signs and symptoms of uveitis . Arch Ophthalmol . 1959;;47:155-170.
Nussenblatt RB, Palestine AG, Chan CC, Roberge F.  Standardization of vitreal inflammatory activity in intermediate and posterior uveitis . Ophthalmology . 1985;;92:467-471.
Boyd AW, Wawrybe SO, Burns GF, Fecondo JV.  Intercellular adhesion molecule-1 (ICAM-1) has a central role in cell-cell contact mediated immune mechanisms . Proc Natl Acad Sci U S A . 1988;;85:3095-3099.
Bevilacqua MP, Stengelin S, Gimbrone MA, Seed B.  Endothelial leukocyte adhesion molecule-1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins . Science . 1989;;243:1160-1165.
Abi Hanna D, McCluskey P, Wakefield D.  HLA antigens in the iris and aqueous humor gamma interferon levels in anterior uveitis . Invest Ophthalmol Vis Sci . 1989;;30:990-995.
Deschenes J, Char DH, Freeman W, Nozik R, Garovoy M.  Uveitis: lymphocyte subpopulation studies . Eye . 1986;;105:246-249.
Deschenes J, Char DH, Kaleta S.  Activated T lymphocytes in uveitis . Br J Ophthalmol . 1988;;72:83-87.
Albelda SA, Buck CA.  Integrins and other cell adhesion molecules . FASEB J . 1990;;4:2868-2880.
Wuthrich RP, Jevnikar AM, Takei R, Lincher LH, Kelly VE.  Intercellular adhesion molecule-1 (ICAM-1) expression is upregulated in autoimmune murine lupus nephritis . Am J Pathol . 1990;;136:2-6.
Dustin ML, Rothlein R, Bhan AK, Dinarello CA, Springer TA.  Induction by IL-1 and interferon-gamma, tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1) . J Immunol . 1986;;137:245-254.
Mantovani A, Dejana E.  Cytokines as communication signals between leukocytes and endothelial cells . Immunol Today . 1989;;11:370-372.
Springer TA, Dustin ML, Kishimoto TK, Marlin S.  The lymphocyte function associated antigen LFA-1, CD2, and LFA-3 molecules: cell adhesion receptors of the immune system . Annu Rev Immunol . 1987;;5:223-252.
Bevilacqua MP, Pober JS, Mendrick DL, Cotran RS, Gimbrone MA.  Identification of an inducible endothelial leukocyte adhesion molecule . Proc Natl Acad Sci U S A . 1987;;84:9238-9242.
Osborn L.  Leukocyte adhesion to endothelium in inflammation . Cell . 1990;;62:3-6.
Doyle C, Strominger JL.  Interaction between CD4 and class II MHC molecules mediated cell adhesion . Nature . 1987;;330:256-259.

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