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

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-gamma), IL-4, IL-5, IL-6, IL-10, GM-CSF, tumour necrosis factor-alpha (TNF-alpha) or TNF-beta, 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 restimulation under conditions which did not activate normal cells. By this approach 168 +/- 120 cells/10,000 peripheral blood mononuclear cells produced IFN-gamma as compared with 10 +/- 8 cells/10,000 non-stimulated cultured cells obtained from IM patients (P < 0.001) and 1/10,000 cells obtained from healthy controls, respectively. No induced production of IL-2, IL-3, IL-4, IL-5, IL-10, GM-CSF or TNF-beta was detected in IM cells obtained from peripheral blood by this restimulation. In contrast, a spontaneous cytokine production was evident in tonsil material obtained from four IM patients tonsilectomized because of respiratory obstruction. From this site 160 +/- 40 cells/10,000 cells produced IL-2, 40 +/- 30 cells IL-6, 30 +/- 30 cells TNF-beta and 35 +/- 25 cells IFN-gamma, respectively. No such spontaneous IL-2, IL-6, TNF-beta or IFN-gamma production was evident in control cells obtained from patients tonsilectomized because of chronic tonsil hyperplasia.