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IFN-γ is only partially restored by co-stimulation with IL-12, IL-2, IL-15, IL-18 or engagement of CD28


Jung Novartis Research Institute, CMB Unit, Brunner Str. 59, A-1235 Vienna, Austria.



Although it is well established that T cells derived from patients with atopic diseases produce low levels of interferon-gamma (IFN-γ), the mechanisms responsible for this phenomenon are poorly understood.


To elucidate whether IFN-γ production may be restored by co-stimulatory molecules known to increase IFN-γ production in vitro. Further, to investigate whether deficient IFN-γ production is associated with disease activity.


Purified peripheral T cells obtained from patients with severe atopic dermatitis (AD), individuals with a history but no symptoms of AD and healthy control subjects were activated with anti-CD3 MoAbs in the presence or absence of anti-CD28 MoAbs, interleukin (IL-) 12, IL-2, IL-15 or IL-18. IFN-γ production was determined at the single cell level by flow cytometry, as well as by ELISA.


Activated T cells from patients with severe AD produced less IFN-γ than T cells from healthy control individuals. IL-12 or engagement of CD28 enhanced IFN-γ production in both healthy and atopic T cells. However, absolute values of IFN-γ were still different. IL-2, IL-15 and IL-18 did not restore IFN-γ production. T cells from individuals with a history of AD produced more IFN-γ than those from subjects with severe AD, but less than T cells from healthy individuals. Atopic T cells expressed regular levels of CD3, CD28 and Stat4, the main signal transducer and activator of transcription for IL-12. IL-4, IL-10 and TGF-β production by T cells were not different between healthy and atopic individuals.


IFN-γ deficiency in atopic T cells is not due to a lack of responsiveness to CD28, IL-12, IL-2, IL-15 or IL-18. T cell-derived cytokines able to antagonize IFN-γ do not contribute to decreased IFN-γ production. The extent of IFN-γ deficiency seems to be dependent on disease activity.

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