Engagement of CD30 shapes the secretion of cytokines by human γ δ 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 γ δ T cells. Elevated surface levels of this molecule persisted in long‐term cultures of γ δ cells, without further cell stimulation. CD30 acted as a co‐stimulus in γ δ 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 γ δ 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.

CD30 ligation differentially affects CXCR4‐dependent HIV‐1 replication and soluble CD30 secretion in non‐Hodgkin cell lines and in γ δ T lymphocytes

“…CD30 is expressed and functionally costimulates secretion of Th0 cytokines and selected chemokines in peripheral V + 9/ Vˇ2 T cell lymphocytes [10]. We here show that engagement of CD30 alone is sufficient to enhance sCD30 secretion in a primary +ˇT cell clone; furthermore, CD3 activation strongly increases sCD30 release, which is further augmented by concomitant CD30 engagement, accordingly with modulation of surface CD30 expression.…”

“…We then analyzed primary +ˇT lymphocytes, in which we have previously shown that CD30 acts as a costimulatory molecule together with anti-CD3 mAb for the release of several cytokines and chemokines [10]. +ˇT cells were stimulated with PMA and immobilized anti-CD3 mAb in the presence or absence of immobilized anti-CD30 mAb.…”

“…It is endowed with costimulatory function in both § g and +ˇT lymphocytes [9,10]. It is, although controversially [11], a marker preferentially expressed by Th2 lymphocytes [12].…”

A matter of life and death: More members of the TNF receptor family join human γδ T lymphocytes

“…We have previously contributed to the understanding of the TNF-R family in gd T-cell biology by demonstrating that CD30, another TNF-R family member, acts as a potent co-stimulator of chemokine and cytokine production in TCR-triggered gd T-cell clones [4]. CD30 was not only expressed on the cell surface of the gd T-cell clones, but was also released as a soluble form (sCD30) upon TCR triggering [5].…”

“…CD30 was not only expressed on the cell surface of the gd T-cell clones, but was also released as a soluble form (sCD30) upon TCR triggering [5]. Notably, CD30 expression was particularly persistent in long-term cultured gd T-cell clones as compared with the other members of the TNF-R family that were evaluated (CD27, 41BB, CD40, TNF-R I, TNF-R II, TNF-R related protein) ( [4] and Fig. 1A).…”