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

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.