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

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.