T. Jung et al., IFN-gamma is only partially restored by co-stimulation with IL-12, IL-2, IL-15, IL-18 or engagement of CD28, CLIN EXP AL, 29(2), 1999, pp. 207-216
Background Although it is well established that T cells derived from patien
ts with atopic diseases produce low levels of interferon-gamma (IFN-gamma),
the mechanisms responsible for this phenomenon are poorly understood.
Objectives To elucidate whether lFN-gamma production may be restored by co-
stimulatory molecules known to increase IFN-gamma production in vitro. Furt
her, to investigate whether deficient IFN-gamma production is associated wi
th disease activity.
Methods Purified peripheral T cells obtained from patients with severe atop
ic dermatitis (AD), individuals with a history but no symptoms of AD and he
althy control subjects were activated with anti-CD3 MoAbs in the presence o
r absence of anti-CD28 MoAbs, interleukin (IL-) 12, IL-2, IL-15 or IL-18. I
FN-gamma production was determined at the single cell level by flow cytomet
ry, as well as by ELISA.
Results Activated T cells from patients with severe AD produced less IFN-ga
mma than T cells from healthy control individuals. IL-12 or engagement of C
D28 enhanced IFN-gamma production in both healthy and atopic T cells. Howev
er, absolute values of IFN-gamma were still different. IL-2, IL-15 and IL-1
8 did not restore IFN-gamma production. T cells from individuals with a his
tory of AD produced more IFN-gamma than those from subjects with severe AD,
but less than T cells from healthy individuals. Atopic T cells expressed r
egular levels of CD3, CD28 and Stat4, the main signal transducer and activa
tor of transcription for IL-12. IL-4, IL-10 and TGF-beta production by T ce
lls were not different between healthy and atopic individuals.
Conclusion IFN-gamma deficiency in atopic T cells is not due to a lack of r
esponsiveness to CD28, IL-12, IL-2, IL-15 or IL-18. T cell-derived cytokine
s able to antagonize IFN-gamma do not contribute to decreased IFN-gamma pro
duction. The extent of IFN-gamma deficiency seems to be dependent on diseas
e activity.