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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
Author(s) -
Thomas Jung,
K Witzak,
K Dieckhoff,
Karolin Zachmann,
Stefanie Heidrich,
Gregorio Aversa,
Christine Neumann
Publication year - 1999
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1046/j.1365-2222.1999.00482.x
Subject(s) - immunology , stimulation , interleukin , medicine , cytokine , endocrinology
Background 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. Objectives 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. Methods 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. Results 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. Conclusion 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.