Mechanisms of deficient interferon-gamma production in atopic diseases

Background The mechanisms responsible for an imbalanced cytokine response i n atopic diseases are still not understood. While impaired interferon-gamma (IFN-gamma) production may be the result of a pathological T-cell/antigen- presenting cell (APC) interaction, evidence was provided that the T cell it self may have an intrinsic defect to produce IFN-gamma. Objective To clarify whether impaired IFN-gamma production by T cells from patients with atopic dermatitis (AD) represents an intrinsic defect in prod ucing IFN-gamma. Methods Effector T cells were generated from CD4(+) CD45RA(+)-naive precurs ors from patients with AD and healthy control individuals by activation wit h anti-CD3(+) anti-CD28 MoAbs. Following restimulation, IFN-gamma productio n was measured by ELISA and flow cytometry. Results IFN-gamma 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-gamma production. Conversion of naive CD45RA(+) to CD45R0(+) effector cells did not differ between atopic and healthy donors' T cells. Conclusion Impaired IFN-gamma production by T cells from atopic individuals is not the result of an intrinsic, genetically fixed, defect to produce su fficient amounts of IFN-gamma. The data provides evidence that correction o f an impaired TH1 response in AD may be successful at the precursor T cell level.