Biswas P, Rovere P, De Filippi C, Heltai S, Smith C, Dagna L, Poli G, Manfredi A A, Ferrarini M
AIDS Immunopathogenesis Unit, Scientific Institute H. S. Raffaele, Milano, Italy.
Eur J Immunol. 2000 Aug;30(8):2172-80. doi: 10.1002/1521-4141(2000)30:8<2172::AID-IMMU2172>3.0.CO;2-P.
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 gamma delta T cells. Elevated surface levels of this molecule persisted in long-term cultures of gamma delta cells, without further cell stimulation. CD30 acted as a co-stimulus in gamma delta T cells by potentiating the intracellular Ca(2+) 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-gamma but not IL-10. The CC chemokines RANTES and macrophage inflammatory protein-1beta 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 gamma delta 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是肿瘤坏死因子受体超家族的成员,先前已证明其在霍奇金淋巴瘤细胞和正常活化淋巴细胞上表达。我们在此表明,CD30在最近活化的人γδT细胞上高度表达。在γδ细胞的长期培养中,该分子的表面水平持续升高,无需进一步的细胞刺激。CD30通过增强CD3交联诱导的细胞内Ca(2+)通量,在γδT细胞中作为共刺激因子发挥作用。CD30的结合增强了CD3刺激后诱导的几种细胞因子的表达,如IL-4和IFN-γ,但不包括IL-10。CC趋化因子RANTES和巨噬细胞炎性蛋白-1β组成性表达,不受刺激影响。中性粒细胞趋化因子IL-8的诱导表达以及CC趋化因子I-309和MDC的诱导表达通过CD30共刺激增强,而未检测到单核细胞趋化蛋白-1的分泌。因此,CD30的触发可能调节γδ细胞释放的几种细胞因子的表达;其生理配体在感染部位由抗原呈递细胞和中性粒细胞表达,可能有助于确定免疫反应的结果。