Mechanisms of deficient interferon-γ production in atopic diseases


Jung Novartis Research Institute, Molecular and Cellular Biology Unit, Brunner Str. 59, A-1235 Vienna, Austria.



The mechanisms responsible for an imbalanced cytokine response in atopic diseases are still not understood. While impaired interferon-gamma (IFN-γ) production may be the result of a pathological T-cell/antigen-presenting cell (APC) interaction, evidence was provided that the T cell itself may have an intrinsic defect to produce IFN-γ.


To clarify whether impaired IFN-γ production by T cells from patients with atopic dermatitis (AD) represents an intrinsic defect in producing IFN-γ.


Effector T cells were generated from CD4+ CD45RA+-naive precursors from patients with AD and healthy control individuals by activation with anti-CD3+ anti-CD28 MoAbs. Following restimulation, IFN-γ production was measured by ELISA and flow cytometry.


IFN-γ production by atopic T cells was decreased compared with healthy T cells. IL-12 present at priming or high doses of IL-2 during the culture period, even in the absence of IL-12, completely restored IFN-γ production. Conversion of naive CD45RA+ to CD45R0+ effector cells did not differ between atopic and healthy donors' T cells.


Impaired IFN-γ production by T cells from atopic individuals is not the result of an intrinsic, genetically fixed, defect to produce sufficient amounts of IFN-γ. The data provides evidence that correction of an impaired TH1 response in AD may be successful at the precursor T cell level.