Interferon-γ secretion of peripheral blood CD8+ T lymphocytes in patients with bronchial asthma: In vitro stimulus determines cytokine production

Abstract

Summary It has been postulated that T lymphocytes orchestrate the chronic inflammation in bronchial asthma. In animal models, infiltration of CD8+ T lymphocytes into the bronchial mucosa prevented bronchial hyperresponsiveness and decreased early and late phase reaction. IFN-γ antagonizes IL-4-dependent IgE production as well as IL-5-induced proliferation and activation of eosinophils. We therefore investigated the secretion of IFN-γ of isolated CD8+ T lymphocytes from peripheral blood of patients with allergic asthma (n = 6) and from healthy controls (n = 7) in vitro. In this setting we compared the effect of stimulation with anti-CD3 antibodies with that of phorbol myristate acetate (PMA) and calcium-ionophore. As expected, CD8+ T lymphocytes from peripheral blood of healthy volunteers produced significantly more IFN-γ in the presence of PMA and calcium-ionophore than after stimulation with anti-CD3 antibodies. However, in subjects with allergic asthma, IFN-γ secretion of CD8+ T cells was significantly higher when incubated with anti-CD3 antibodies than after activation with PMA and calcium-ionophore. While IFN-γ secretion of CD8+ T lymphocytes of patients with allergic asthma was lower than that of healthy controls in the presence of PMA/calcium-ionophore, it was significantly elevated when compared with normal controls after stimulation with anti-CD3 antibodies. Thus, potent activators of cytokine secretion, such as PMA and calcium-ionophore, induce a cytokine profile different from that induced by weaker stimulants, such as anti-CD3 antibodies. These findings have implications for further studies investigating cytokine production of inflammatory cells in vitro.