CD69 expression on peripheral CD4+ T cells parallels disease activity and is reduced by mycophenolate mofetil therapy in uveitis

D. J. Kilmartin, Z. J. Fletcher, J. A. Almeida, Janet Mary Liversidge, John Vincent Forrester, A. D. Dick

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Abstract

PURPOSE. To assess the effects of mycophenolate mofetil (MMF) therapy on T helper cell activation status, using CD69 expression and cytokine profile with flow cytometry in relation to clinical activity in uveitis.

METHODS. Patients with posterior or intermediate uveitis treated with MMF (n = 10), patients with active uveitis not treated with MMF and receiving no or minimal therapy (n = 10), and healthy volunteers (n = 21) had peripheral blood lymphocyte immunofluorescence analysis for T helper cell (CD4, CD3) markers, activation status (CD69), and intracellular cytokine (interleukin [IL]-2, interferon [IFN]-gamma, and IL-4) levels. Patients were compared before and during MMF therapy in relation to T helper cell activation and clinical activity.

RESULTS. Patients with active uveitis not treated with MMF and receiving no or minimal therapy had increased frequency of CD69-positive CD4 T cells (10.5% +/- 4.6%, P = 0.0007) compared with healthy volunteers (3.3% +/- 2.7%). Of all patients receiving MMF therapy, only patients with moderate to severe uveitis activity in the pre-MMF treatment group (n = 5; 15.5% +/- 5.0%, P = 0.004) had increased frequency of CD69-positive CD4 T cells compared with healthy volunteers. During MMF therapy, a significant reduction in frequency of CD69-positive CD4 T cells occurred in patients with prior moderate to severe uveitis activity (to 8.9% +/- 3.8%, P = 0.04). Levels of GD69-positive CD4 T cells in patients who had had inactive or mildly active disease (n = 5) before and during MMF therapy were comparable with levels in healthy volunteers. No significant changes in cytokine levels were found between the patient and control groups. A significant association between changes in frequency of CD69-positive CD4 T cells and changes in visual acuity (P = 0.008) and changes in vitreal haze (binocular indirect ophthalmoscopy score; P = 0.01) was observed in MMF-treated patients with prior moderate to severe uveitis activity.

CONCLUSIONS. Reduction in uveitis activity during MMF therapy correlates with reduction in frequency of peripheral blood CD69-positive CD4 cells. The frequency of CD69-positive CD4 T cells is a measure of activity in posterior uveitis and may guide adequate immunosuppression.

Original languageEnglish
Pages (from-to)1285-1292
Number of pages7
JournalInvestigative Ophthalmology & Visual Science
Volume42
Issue number6
Publication statusPublished - 2001

Keywords

  • FREQUENCIES

Cite this

Kilmartin, D. J., Fletcher, Z. J., Almeida, J. A., Liversidge, J. M., Forrester, J. V., & Dick, A. D. (2001). CD69 expression on peripheral CD4+ T cells parallels disease activity and is reduced by mycophenolate mofetil therapy in uveitis. Investigative Ophthalmology & Visual Science, 42(6), 1285-1292.

CD69 expression on peripheral CD4+ T cells parallels disease activity and is reduced by mycophenolate mofetil therapy in uveitis. / Kilmartin, D. J.; Fletcher, Z. J.; Almeida, J. A.; Liversidge, Janet Mary; Forrester, John Vincent; Dick, A. D.

In: Investigative Ophthalmology & Visual Science, Vol. 42, No. 6, 2001, p. 1285-1292.

Research output: Contribution to journalArticle

Kilmartin, DJ, Fletcher, ZJ, Almeida, JA, Liversidge, JM, Forrester, JV & Dick, AD 2001, 'CD69 expression on peripheral CD4+ T cells parallels disease activity and is reduced by mycophenolate mofetil therapy in uveitis', Investigative Ophthalmology & Visual Science, vol. 42, no. 6, pp. 1285-1292.
Kilmartin, D. J. ; Fletcher, Z. J. ; Almeida, J. A. ; Liversidge, Janet Mary ; Forrester, John Vincent ; Dick, A. D. / CD69 expression on peripheral CD4+ T cells parallels disease activity and is reduced by mycophenolate mofetil therapy in uveitis. In: Investigative Ophthalmology & Visual Science. 2001 ; Vol. 42, No. 6. pp. 1285-1292.
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title = "CD69 expression on peripheral CD4+ T cells parallels disease activity and is reduced by mycophenolate mofetil therapy in uveitis",
abstract = "PURPOSE. To assess the effects of mycophenolate mofetil (MMF) therapy on T helper cell activation status, using CD69 expression and cytokine profile with flow cytometry in relation to clinical activity in uveitis.METHODS. Patients with posterior or intermediate uveitis treated with MMF (n = 10), patients with active uveitis not treated with MMF and receiving no or minimal therapy (n = 10), and healthy volunteers (n = 21) had peripheral blood lymphocyte immunofluorescence analysis for T helper cell (CD4, CD3) markers, activation status (CD69), and intracellular cytokine (interleukin [IL]-2, interferon [IFN]-gamma, and IL-4) levels. Patients were compared before and during MMF therapy in relation to T helper cell activation and clinical activity.RESULTS. Patients with active uveitis not treated with MMF and receiving no or minimal therapy had increased frequency of CD69-positive CD4 T cells (10.5{\%} +/- 4.6{\%}, P = 0.0007) compared with healthy volunteers (3.3{\%} +/- 2.7{\%}). Of all patients receiving MMF therapy, only patients with moderate to severe uveitis activity in the pre-MMF treatment group (n = 5; 15.5{\%} +/- 5.0{\%}, P = 0.004) had increased frequency of CD69-positive CD4 T cells compared with healthy volunteers. During MMF therapy, a significant reduction in frequency of CD69-positive CD4 T cells occurred in patients with prior moderate to severe uveitis activity (to 8.9{\%} +/- 3.8{\%}, P = 0.04). Levels of GD69-positive CD4 T cells in patients who had had inactive or mildly active disease (n = 5) before and during MMF therapy were comparable with levels in healthy volunteers. No significant changes in cytokine levels were found between the patient and control groups. A significant association between changes in frequency of CD69-positive CD4 T cells and changes in visual acuity (P = 0.008) and changes in vitreal haze (binocular indirect ophthalmoscopy score; P = 0.01) was observed in MMF-treated patients with prior moderate to severe uveitis activity.CONCLUSIONS. Reduction in uveitis activity during MMF therapy correlates with reduction in frequency of peripheral blood CD69-positive CD4 cells. The frequency of CD69-positive CD4 T cells is a measure of activity in posterior uveitis and may guide adequate immunosuppression.",
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TY - JOUR

T1 - CD69 expression on peripheral CD4+ T cells parallels disease activity and is reduced by mycophenolate mofetil therapy in uveitis

AU - Kilmartin, D. J.

AU - Fletcher, Z. J.

AU - Almeida, J. A.

AU - Liversidge, Janet Mary

AU - Forrester, John Vincent

AU - Dick, A. D.

PY - 2001

Y1 - 2001

N2 - PURPOSE. To assess the effects of mycophenolate mofetil (MMF) therapy on T helper cell activation status, using CD69 expression and cytokine profile with flow cytometry in relation to clinical activity in uveitis.METHODS. Patients with posterior or intermediate uveitis treated with MMF (n = 10), patients with active uveitis not treated with MMF and receiving no or minimal therapy (n = 10), and healthy volunteers (n = 21) had peripheral blood lymphocyte immunofluorescence analysis for T helper cell (CD4, CD3) markers, activation status (CD69), and intracellular cytokine (interleukin [IL]-2, interferon [IFN]-gamma, and IL-4) levels. Patients were compared before and during MMF therapy in relation to T helper cell activation and clinical activity.RESULTS. Patients with active uveitis not treated with MMF and receiving no or minimal therapy had increased frequency of CD69-positive CD4 T cells (10.5% +/- 4.6%, P = 0.0007) compared with healthy volunteers (3.3% +/- 2.7%). Of all patients receiving MMF therapy, only patients with moderate to severe uveitis activity in the pre-MMF treatment group (n = 5; 15.5% +/- 5.0%, P = 0.004) had increased frequency of CD69-positive CD4 T cells compared with healthy volunteers. During MMF therapy, a significant reduction in frequency of CD69-positive CD4 T cells occurred in patients with prior moderate to severe uveitis activity (to 8.9% +/- 3.8%, P = 0.04). Levels of GD69-positive CD4 T cells in patients who had had inactive or mildly active disease (n = 5) before and during MMF therapy were comparable with levels in healthy volunteers. No significant changes in cytokine levels were found between the patient and control groups. A significant association between changes in frequency of CD69-positive CD4 T cells and changes in visual acuity (P = 0.008) and changes in vitreal haze (binocular indirect ophthalmoscopy score; P = 0.01) was observed in MMF-treated patients with prior moderate to severe uveitis activity.CONCLUSIONS. Reduction in uveitis activity during MMF therapy correlates with reduction in frequency of peripheral blood CD69-positive CD4 cells. The frequency of CD69-positive CD4 T cells is a measure of activity in posterior uveitis and may guide adequate immunosuppression.

AB - PURPOSE. To assess the effects of mycophenolate mofetil (MMF) therapy on T helper cell activation status, using CD69 expression and cytokine profile with flow cytometry in relation to clinical activity in uveitis.METHODS. Patients with posterior or intermediate uveitis treated with MMF (n = 10), patients with active uveitis not treated with MMF and receiving no or minimal therapy (n = 10), and healthy volunteers (n = 21) had peripheral blood lymphocyte immunofluorescence analysis for T helper cell (CD4, CD3) markers, activation status (CD69), and intracellular cytokine (interleukin [IL]-2, interferon [IFN]-gamma, and IL-4) levels. Patients were compared before and during MMF therapy in relation to T helper cell activation and clinical activity.RESULTS. Patients with active uveitis not treated with MMF and receiving no or minimal therapy had increased frequency of CD69-positive CD4 T cells (10.5% +/- 4.6%, P = 0.0007) compared with healthy volunteers (3.3% +/- 2.7%). Of all patients receiving MMF therapy, only patients with moderate to severe uveitis activity in the pre-MMF treatment group (n = 5; 15.5% +/- 5.0%, P = 0.004) had increased frequency of CD69-positive CD4 T cells compared with healthy volunteers. During MMF therapy, a significant reduction in frequency of CD69-positive CD4 T cells occurred in patients with prior moderate to severe uveitis activity (to 8.9% +/- 3.8%, P = 0.04). Levels of GD69-positive CD4 T cells in patients who had had inactive or mildly active disease (n = 5) before and during MMF therapy were comparable with levels in healthy volunteers. No significant changes in cytokine levels were found between the patient and control groups. A significant association between changes in frequency of CD69-positive CD4 T cells and changes in visual acuity (P = 0.008) and changes in vitreal haze (binocular indirect ophthalmoscopy score; P = 0.01) was observed in MMF-treated patients with prior moderate to severe uveitis activity.CONCLUSIONS. Reduction in uveitis activity during MMF therapy correlates with reduction in frequency of peripheral blood CD69-positive CD4 cells. The frequency of CD69-positive CD4 T cells is a measure of activity in posterior uveitis and may guide adequate immunosuppression.

KW - FREQUENCIES

M3 - Article

VL - 42

SP - 1285

EP - 1292

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

SN - 0146-0404

IS - 6

ER -