Engagement of CD30 shapes the secretion of cytokines by human γδ T cells

Abstract

CD30 is a member of the TNF receptor superfamily, previously shown to be expressed on Hodgkin's lymphoma cells and on normal activated lymphocytes. We here show that CD30 is highly expressed on recently activated human γδ T cells. Elevated surface levels of this molecule persisted in long-term cultures of γδ cells, without further cell stimulation. CD30 acted as a co-stimulus in γδ T cells by potentiating the intracellular Ca2+ fluxes induced by CD3 cross-linking. The engagement of CD30 enhanced the expression of several cytokines induced upon CD3 stimulation such as IL-4 and IFN-γ but not IL-10. The CC chemokines RANTES and macrophage inflammatory protein-1β 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 chemokines I-309 and MDC, whereas the secretion of the monocyte chemotactic protein-1 was not detected. Triggering of CD30 may therefore modulate the expression of several cytokines released by γδ cells; the expression of its physiologic ligand by APC and neutrophils at the site of infection may contribute to determine the outcome of an immune response.