2007, Number 1
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Rev Mex Oftalmol 2007; 81 (1)
Valoración de la respuesta inmunológica sistémica en pacientes con queratitis herpética
Aguilar-Velázquez G, Santacruz-Valdés C, Chávez R, Estrada-García I, Estrada-Parra S, Jiménez-Martínez MC
Language: Spanish
References: 24
Page: 7-13
PDF size: 545.55 Kb.
ABSTRACT
Introduction: T cells play an important role in the immunepathogenesis of herpetic stromal keratitis (HSK). It has been demonstrated, on animal models, that T cells infiltrate the cornea and produce large quantities of IFN-γ. In contrast, the immune response in humans has not been broadly studied.
Aim: To evaluate cytokine profile on peripheral blood mononuclear cells (PBMC) from HSK patients (p).
Methods: We determined on PBMC from HSK-p and healthy controls (HC) the expression of CD4, CD8, intracellular cytokines (IFN-γ/IL-4) and proinflammatory cytokines (TNF-α/IL-6/IL-1b) in culture supernatants (SN) before/after polyclonal stimuli. Results were obtained by flow-cytometry and ELISA.
Results: Percentage (%) of CD4
+IFN-γ
+ T cells in HSK-p 16 vs 8 in HC (p=0.024); % of CD4
+IL-4
+ T cells in HSK-p 7 vs 4 in
HC; % of CD8
+IFN-γ
+ T cells in HSK-p 33 vs 31 in HC; % of CD8
+IL-4
+ T cells in HSK-p 5 vs 6 in HC; % of CD4
+IL 4
+ T cells 7 vs 16 CD4
+IFN-γ
+ T cells from HSK-p (p=0.006). Cytokines in SN (pg/ml): TNF-α in non stimulated cells (NSC) from HSKp
285 vs 3740 in stimulated cells (SC) from HSK-p (p‹0.001); TNF-α in NSC from HC 172 vs 3364 in SC from HC (p‹0.001); IL-1β in NSC from HSK-p 53 vs 107 in SC from HSK-p (p=0.038); IL-1β in NSC from HC 37 vs 54 in SC from HC; IL-1β in SC from HSK-p 107 vs 54 in SC from HC (p=0.029); IL-6 in NSC from HSK-p 328 vs 481 in SC from HSK-p (p=0.026).
Conclusions: Stimulated T cells from HSK-p were predominantly IFN-γ
+. It is well known that IFN-γ induces production of proinflammatory cytokines from activated macrophages, in our study we find IL-1b as the most important proinflammatory cytokine increased after
in vitro stimuli in patients with herpetic stromal keratitis. These results suggest that peripheral IFN-γ
+ cells could migrate to the human cornea and to collaborate with residents or infiltrating cells to produce proinflammatory cytokines, increasing the inflammatory damage as it has been demonstrated in animal models.
REFERENCES
Carr DJ, Harle P, Gebhardt BM. The immune response to ocular herpes simplex virus type 1 infection. Exp Biol Med 2001; 226(5):353-66.
Deshpande SP, Zheng M, Lee S, Rouse BT. Mechanisms of pathogenesis in herpetic immunoinflammatory ocular lesions. Vet Microbiol 2002; 86(1-2):17-26.
Naito J, Mott KR, Osorio N, Jin L, Perng GC. Herpes simplex virus type 1 immediate-early protein ICP0 diffuses out of infected rabbit corneas. J Gen Virol 2005; 86(11):2979-88.
Thomas J, Gangappa S, Kanangat S, Rouse BT. On the essential involvement of neutrophils in the immunopathologic disease: herpetic stromal keratitis. J Immunol 1997; 158(3):1383-91.
Gangappa S, Deshpande SP, Rouse BT. Bystander activation of CD4+ T cells accounts for herpetic ocular lesions. Invest Ophthalmol Vis Sci 2000; 41(2):453-9.
Mal’khanov VB. "Active" rosette-forming T-lymphocytes in ocular herpes. Vopr Virusol 1981; 4(4):493-5.
Saini JS, Datta U, Pradhan D. Cell mediated immunity in herpes simplex keratitis in man. Acta Ophthalmol (Copenh) 1990; 68(5):519-24.
Newell CK, Sendele D, Rouse BT. Effects of CD4+ and CD8+ T-lymphocyte depletion on the induction and expression of herpes simplex stromal keratitis. Reg Immunol 1989; 2(6):366-9.
Mercadal CM, Bouley DM, DeStephano D, Rouse BT. Herpetic stromal keratitis in the reconstituted scid mouse model. J Virol 1993; 67(6):3404-8.
Biswas PS, Banerjee K, Kim B, Smith J, Rouse BT. A novel flow cytometry based assay for quantification of corneal angiogenesis in the mouse model of herpetic stromal keratitis. Exp Eye Res 2005; 80(1):73-81.
Hendricks RL, Tumpey TM. Contribution of virus and immune factors to herpes simplex virus type I-induced corneal pathology. Invest Ophthalmol Vis Sci 1990; 31(10):1929–1939
Meyers-Elliott RH, Chitjian PA. Immunopathogenesis of corneal inflammation in herpes simplex virus stromal keratitis: role of the polymorphonuclear leukocyte. Invest Ophthalmol Vis Sci 1981; 20(6):784-98.
Shimeld C, Whiteland JL, Nicholls SM, Easty DL, Hill TJ. Immune cell infiltration in corneas of mice with recurrent herpes simplex virus disease. J Gen Virol 1996; 77(5):977–985.
Miller JK, Laycock KA, Nash MM, Pepose JS. Corneal Langerhans cell dynamics after herpes simplex virus reactivation. Invest Ophthalmol Vis Sci 1993; 34(7): 2282–2290.
Verjans GM, Remeijer L, van Binnendijk RS, Cornelissen JGC, Volker-Dieben HJ, Baarsma SG, Osterhaus ADME. Identification and characterization of herpes simple virus-specific CD4+ T cells in corneas of herpetic stromal keratitis patients. J Infect Dis 1998; 177(2):484–488.
Thomas J, Kanangat S, Rouse BT. Herpes simplex virus replication- induced expression of chemokines and proinflammatory cytokines in the eye: implications in herpetic stromal keratitis. J Interferon Cytokine Res 1998; 18(9):681-690.
Watford WT, Moriguchi M, Morinobu A, O’Shea JJ. The biology of IL-12: coordinating innate and adaptive immune responses. Cytokine Growth Factor Rev 2003; 14(5):361-368.
Foster B, Prussin C. Detection of Intracellular Cytokines by Flow Cytometry. Curr Prot Immunol 2002; 6:1-16.
Thomson A. The cytokine Handbook. Academia Press; 1998.
Minami M, Kita M, Yan XQ, Yamamoto T, Iida T, Sekikawa K, Iwakura Y, Imanishi J. Role of IFN-gamma and tumor necrosis factor-alpha in herpes simplex virus type 1 infection. J Interferon Cytokine Res 2002; 22(6):671-6.
Staats HF, Lausch RN. Cytokine expression in vivo during murine herpetic stromal keratitis. Effect of protective antibody therapy. J Immunol 1993; 151(1):277-83.
Keadle TL, Usui N, Laycock KA, Miller JK, Pepose JS, Stuart PM. IL-1 and TNF-alpha are important factors in the pathogenesis of murine recurrent herpetic stromal keratitis. Invest Ophthalmol Vis Sci 2000; 41(1):96-102.
Fenton RR, Molesworth-Kenyon S, Oakes JE, Lausch RN. Linkage of IL-6 with neutrophil chemoattractant expression in virus-induced ocular inflammation. Invest Ophthalmol Vis Sci 2002; 43(3):737-43.
Biswas PS, Banerjee K, Kinchington PR, Rouse BT. Involvement of IL-6 in the paracrine production of VEGF in ocular HSV-1 infection. Exp Eye Res 2006; 82 (1):46-54.