Dj. Kilmartin et al., CD69 expression on peripheral CD4(+) T cells parallels disease activity and is reduced by mycophenolate mofetil therapy in uveitis, INV OPHTH V, 42(6), 2001, pp. 1285-1292
PURPOSE. To assess the effects of mycophenolate mofetil (MMF) therapy on T
helper cell activation status, using CD69 expression and cytokine profile w
ith 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 periphera
l 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 b
efore and during MMF therapy in relation to T helper cell activation and cl
inical 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 (1
0.5% +/- 4.6%, P = 0.0007) compared with healthy volunteers (3.3% +/- 2.7%)
. Of all patients receiving MMF therapy, only patients with moderate to sev
ere 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 w
ith healthy volunteers. During MMF therapy, a significant reduction in freq
uency 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-po
sitive CD4 T cells in patients who had had inactive or mildly active diseas
e (n = 5) before and during MMF therapy were comparable with levels in heal
thy volunteers. No significant changes in cytokine levels were found betwee
n 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 sco
re; P = 0.01) was observed in MMF-treated patients with prior moderate to s
evere uveitis activity.
CONCLUSIONS. Reduction in uveitis activity during MMF therapy correlates wi
th reduction in frequency of peripheral blood CD69-positive CD4 cells. The
frequency of CD69-positive CD4 T cells is a measure of activity in posterio
r uveitis and may guide adequate immunosuppression.