Engagement of CD30 shapes the secretion of cytokines by human gamma delta T cells

CD30 is a member of the TNF receptor superfamily, previously shown to be ex pressed on Hodgkin's lymphoma cells and on normal activated lymphocytes. We here show that CD30 is highly expressed on recently activated human gamma delta T cells. Elevated surface levels of this molecule persisted in long-t erm cultures of gamma delta cells, without further cell stimulation. CD30 a cted as a co-stimulus in gamma delta T cells by potentiating the intracellu lar Ca2+ fluxes induced by CD3 cross-linking. The engagement of CD30 enhanc ed the expression of several cytokines induced upon CD3 stimulation such as IL-4 and IFN-gamma but not IL-10. The CC chemokines RANTES and macrophage inflammatory protein-1 beta were constitutively expressed and not affected by stimulation. The inducible expression of the neutrophil chemoattractant IL-8 was enhanced by CD30 co-stimulation, as well as that of the CC chemoki nes I-309 and MDC, whereas the secretion of the monocyte chemotactic protei n-1 was not detected. Triggering of CD30 may therefore modulate the express ion of several cytokines released by gamma delta cells; the expression of i ts physiologic ligand by APC and neutrophils at the site of infection may c ontribute to determine the outcome of an immune response.