Anti-TNFalpha therapy modulates the phenotype of peripheral blood CD4+ T cells in patients with posterior segment intraocular inflammation

Kathrin Greiner, C. C. Murphy, F. Willermain, Linda Duncan, Jarka Plskova, G. Hale, J. D. Isaacs, John Vincent Forrester, A. D. Dick

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

PURPOSE. Posterior segment intraocular inflammation (PSII) is a putative Th1 CD4(+) cell mediated autoimmune disorder. In experimental autoimmune uveoretinitis, neutralization of tumor necrosis factor (TNF)-alpha induces suppression of Th1 cells, macrophage activation, and target organ damage. Previous studies implicated an efficacy of anti-TNFalpha therapies in patients with PSII. This study investigated the immunomodulatory effect of anti-TNFa therapy to find predictors of effective immunosuppression in PSII.

METHODS. Fifteen patients with PSII refractory to conventional immunosuppressive therapy received a single infusion of a recombinant protein generated by fusing the p55 TNFalpha receptor. with human IgG1. During 17 treatment periods, visual acuity (logarithm of the minimum angle of resolution [logMAR]) was monitored as a response criterion. Phenotype markers of CD4(+) T cells were analyzed before and 2, 4, and 12 weeks after therapy. Expression of intracellular cytokines (interferon [IFN]-gamma, interleukin [IL]-10, and TNFa) and Th1/Th2-specific chemokine receptors (CXCR3, CCR4, and CCR5) on peripheral blood CD4(+) T cells was determined using flow cytometry.

RESULTS. The fraction of IL-10 -expressing CD4+ T cells was increased during 12 of 17 treatment periods within 2 weeks after treatment. During eight treatment periods, this increase was associated with an improvement of visual acuity of at least 0.2 logMAR within 4 weeks (P = 0.029). The ratio between IL-10- and IFNgamma- expressing CD4+ T cells was significantly increased 2 weeks after therapy (P = 0.015). There was no significant change of CXCR3, CCR4, or CCR5 expression.

CONCLUSIONS. Neutralizing TNFa activity in PSII increases the fraction of peripheral blood CD4(+) T cells expressing IL-10, which correlates with a recovery of visual function.

Original languageEnglish
Pages (from-to)170-176
Number of pages6
JournalInvestigative Ophthalmology & Visual Science
Volume45
Issue number1
DOIs
Publication statusPublished - 2004

Keywords

  • EXPERIMENTAL AUTOIMMUNE UVEORETINITIS
  • NECROSIS-FACTOR-ALPHA
  • CHEMOKINE RECEPTOR EXPRESSION
  • RHEUMATOID-ARTHRITIS
  • CHEMOTACTIC RESPONSIVENESS
  • OCULAR INFLAMMATION
  • BEHCETS-DISEASE
  • UVEITIS
  • CYTOKINES
  • INHIBITION

Cite this

Anti-TNFalpha therapy modulates the phenotype of peripheral blood CD4+ T cells in patients with posterior segment intraocular inflammation. / Greiner, Kathrin; Murphy, C. C.; Willermain, F.; Duncan, Linda; Plskova, Jarka; Hale, G.; Isaacs, J. D.; Forrester, John Vincent; Dick, A. D.

In: Investigative Ophthalmology & Visual Science, Vol. 45, No. 1, 2004, p. 170-176.

Research output: Contribution to journalArticle

Greiner, K, Murphy, CC, Willermain, F, Duncan, L, Plskova, J, Hale, G, Isaacs, JD, Forrester, JV & Dick, AD 2004, 'Anti-TNFalpha therapy modulates the phenotype of peripheral blood CD4+ T cells in patients with posterior segment intraocular inflammation', Investigative Ophthalmology & Visual Science, vol. 45, no. 1, pp. 170-176. https://doi.org/10.1167/iovs.03-0659
Greiner, Kathrin ; Murphy, C. C. ; Willermain, F. ; Duncan, Linda ; Plskova, Jarka ; Hale, G. ; Isaacs, J. D. ; Forrester, John Vincent ; Dick, A. D. / Anti-TNFalpha therapy modulates the phenotype of peripheral blood CD4+ T cells in patients with posterior segment intraocular inflammation. In: Investigative Ophthalmology & Visual Science. 2004 ; Vol. 45, No. 1. pp. 170-176.
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abstract = "PURPOSE. Posterior segment intraocular inflammation (PSII) is a putative Th1 CD4(+) cell mediated autoimmune disorder. In experimental autoimmune uveoretinitis, neutralization of tumor necrosis factor (TNF)-alpha induces suppression of Th1 cells, macrophage activation, and target organ damage. Previous studies implicated an efficacy of anti-TNFalpha therapies in patients with PSII. This study investigated the immunomodulatory effect of anti-TNFa therapy to find predictors of effective immunosuppression in PSII.METHODS. Fifteen patients with PSII refractory to conventional immunosuppressive therapy received a single infusion of a recombinant protein generated by fusing the p55 TNFalpha receptor. with human IgG1. During 17 treatment periods, visual acuity (logarithm of the minimum angle of resolution [logMAR]) was monitored as a response criterion. Phenotype markers of CD4(+) T cells were analyzed before and 2, 4, and 12 weeks after therapy. Expression of intracellular cytokines (interferon [IFN]-gamma, interleukin [IL]-10, and TNFa) and Th1/Th2-specific chemokine receptors (CXCR3, CCR4, and CCR5) on peripheral blood CD4(+) T cells was determined using flow cytometry.RESULTS. The fraction of IL-10 -expressing CD4+ T cells was increased during 12 of 17 treatment periods within 2 weeks after treatment. During eight treatment periods, this increase was associated with an improvement of visual acuity of at least 0.2 logMAR within 4 weeks (P = 0.029). The ratio between IL-10- and IFNgamma- expressing CD4+ T cells was significantly increased 2 weeks after therapy (P = 0.015). There was no significant change of CXCR3, CCR4, or CCR5 expression.CONCLUSIONS. Neutralizing TNFa activity in PSII increases the fraction of peripheral blood CD4(+) T cells expressing IL-10, which correlates with a recovery of visual function.",
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T1 - Anti-TNFalpha therapy modulates the phenotype of peripheral blood CD4+ T cells in patients with posterior segment intraocular inflammation

AU - Greiner, Kathrin

AU - Murphy, C. C.

AU - Willermain, F.

AU - Duncan, Linda

AU - Plskova, Jarka

AU - Hale, G.

AU - Isaacs, J. D.

AU - Forrester, John Vincent

AU - Dick, A. D.

PY - 2004

Y1 - 2004

N2 - PURPOSE. Posterior segment intraocular inflammation (PSII) is a putative Th1 CD4(+) cell mediated autoimmune disorder. In experimental autoimmune uveoretinitis, neutralization of tumor necrosis factor (TNF)-alpha induces suppression of Th1 cells, macrophage activation, and target organ damage. Previous studies implicated an efficacy of anti-TNFalpha therapies in patients with PSII. This study investigated the immunomodulatory effect of anti-TNFa therapy to find predictors of effective immunosuppression in PSII.METHODS. Fifteen patients with PSII refractory to conventional immunosuppressive therapy received a single infusion of a recombinant protein generated by fusing the p55 TNFalpha receptor. with human IgG1. During 17 treatment periods, visual acuity (logarithm of the minimum angle of resolution [logMAR]) was monitored as a response criterion. Phenotype markers of CD4(+) T cells were analyzed before and 2, 4, and 12 weeks after therapy. Expression of intracellular cytokines (interferon [IFN]-gamma, interleukin [IL]-10, and TNFa) and Th1/Th2-specific chemokine receptors (CXCR3, CCR4, and CCR5) on peripheral blood CD4(+) T cells was determined using flow cytometry.RESULTS. The fraction of IL-10 -expressing CD4+ T cells was increased during 12 of 17 treatment periods within 2 weeks after treatment. During eight treatment periods, this increase was associated with an improvement of visual acuity of at least 0.2 logMAR within 4 weeks (P = 0.029). The ratio between IL-10- and IFNgamma- expressing CD4+ T cells was significantly increased 2 weeks after therapy (P = 0.015). There was no significant change of CXCR3, CCR4, or CCR5 expression.CONCLUSIONS. Neutralizing TNFa activity in PSII increases the fraction of peripheral blood CD4(+) T cells expressing IL-10, which correlates with a recovery of visual function.

AB - PURPOSE. Posterior segment intraocular inflammation (PSII) is a putative Th1 CD4(+) cell mediated autoimmune disorder. In experimental autoimmune uveoretinitis, neutralization of tumor necrosis factor (TNF)-alpha induces suppression of Th1 cells, macrophage activation, and target organ damage. Previous studies implicated an efficacy of anti-TNFalpha therapies in patients with PSII. This study investigated the immunomodulatory effect of anti-TNFa therapy to find predictors of effective immunosuppression in PSII.METHODS. Fifteen patients with PSII refractory to conventional immunosuppressive therapy received a single infusion of a recombinant protein generated by fusing the p55 TNFalpha receptor. with human IgG1. During 17 treatment periods, visual acuity (logarithm of the minimum angle of resolution [logMAR]) was monitored as a response criterion. Phenotype markers of CD4(+) T cells were analyzed before and 2, 4, and 12 weeks after therapy. Expression of intracellular cytokines (interferon [IFN]-gamma, interleukin [IL]-10, and TNFa) and Th1/Th2-specific chemokine receptors (CXCR3, CCR4, and CCR5) on peripheral blood CD4(+) T cells was determined using flow cytometry.RESULTS. The fraction of IL-10 -expressing CD4+ T cells was increased during 12 of 17 treatment periods within 2 weeks after treatment. During eight treatment periods, this increase was associated with an improvement of visual acuity of at least 0.2 logMAR within 4 weeks (P = 0.029). The ratio between IL-10- and IFNgamma- expressing CD4+ T cells was significantly increased 2 weeks after therapy (P = 0.015). There was no significant change of CXCR3, CCR4, or CCR5 expression.CONCLUSIONS. Neutralizing TNFa activity in PSII increases the fraction of peripheral blood CD4(+) T cells expressing IL-10, which correlates with a recovery of visual function.

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KW - NECROSIS-FACTOR-ALPHA

KW - CHEMOKINE RECEPTOR EXPRESSION

KW - RHEUMATOID-ARTHRITIS

KW - CHEMOTACTIC RESPONSIVENESS

KW - OCULAR INFLAMMATION

KW - BEHCETS-DISEASE

KW - UVEITIS

KW - CYTOKINES

KW - INHIBITION

U2 - 10.1167/iovs.03-0659

DO - 10.1167/iovs.03-0659

M3 - Article

VL - 45

SP - 170

EP - 176

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

SN - 0146-0404

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