Characterization of cytokine production in infectious mononucleosis studied at a single-cell level in tonsil and peripheral blood

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Abstract
SUMMARY: Cytokine profile and production was studied at a single-cell level in cells obtained from 14 patients with acute infectious mononucleosis (IM), with less than 7 days of symptomatic disease, by use of cytokine-specific MoAbs and indirect immunofluorescence technique. In producer cells, all the studied cytokines, except IL-1, accumulated in the Golgi system, which resulted in a characteristic morphology of the staining. Less than one in a thousand mononuclear cells obtained directly from IM blood and stained within 2 h of sampling produced IL-2, interferon-gamma (IFN-γ), IL-4, IL-5, IL-6, IL-10, GM-CSF, tumour necrosis factor-alpha (TNF-α) or TNF-β, spontaneously. However, these cells were induced to cytokine synthesis by T cell receptor ligation in vitro using immobilized anti-CD3 MoAbs for 2–3 h restimulalion under conditions which did not activate normal cells. By this approach 168±120 cells/10000 peripheral blood mononuclear cells produced IFN-γ as compared with 10±8 cells/10000 non-stimulated cultured cells obtained from IM patients (P < 0.001) and 1 /10000 cells obtained from healthy controls, respectively. No induced production of IL-2, IL-3, IL-4, IL-5, IL-10, GM-CSF or TNF-β was detected in IM cells obtained from peripheral blood by this restimulalion. In contrast, a spontaneous cylokine production was evident in tonsil material obtained from four IM patients tonsilectomized because of respiratory obstruction. From this site 160±40 cells/10000 cells produced IL-2, 40±30 cells IL-6. 30±30 cells TNF-β and 35±25 cells IFN-γ, respectively. No such spontaneous IL-2, IL-6, TNF-γ or IFN-γ production was evident in control cells obtained from patients tonsilectomized because of chronic tonsil hyperplasia.