A Functional γδTCR/CD3 Complex Distinct from γδT Cells Is Expressed by Human Eosinophils

Abstract

BackgroundEosinophils are effector cells during parasitic infections and allergic responses. However, their contribution to innate immunity has been only recently unravelled.Methodology/Principal FindingsHere we show that human eosinophils express CD3 and γδ T Cell Receptor (TCR) but not αβ TCR. Surface expression of γδTCR/CD3 is heterogeneous between eosinophil donors and inducible by mycobacterial ligands. Surface immunoprecipitation revealed expression of the full γδTCR/CD3 complex. Real-time PCR amplification for CD3, γ and δ TCR constant regions transcripts showed a significantly lower expression in eosinophils than in γδT cells. Limited TCR rearrangements occur in eosinophils as shown by spectratyping analysis of CDR3 length profiles and in situ hybridization. Release by eosinophils of Reactive Oxygen Species, granule proteins, Eosinophil Peroxidase and Eosinophil-Derived Neurotoxin and cytokines (IFN-γ and TNF-α) was observed following activation by γδTCR-specific agonists or by mycobacteria. These effects were inhibited by anti-γδTCR blocking antibodies and antagonists. Moreover, γδTCR/CD3 was involved in eosinophil cytotoxicity against tumor cells.Conclusions/SignificanceOur results provide evidence that human eosinophils express a functional γδTCR/CD3 with similar, but not identical, characteristics to γδTCR from γδT cells. We propose that this receptor contributes to eosinophil innate responses against mycobacteria and tumors and may represent an additional link between lymphoid and myeloid lineages.

Human Eosinophils Exert TNF-α and Granzyme A-Mediated Tumoricidal Activity toward Colon Carcinoma Cells

“…In addition to these adhesion receptors, other membrane receptors participate in this cytotoxicity process. Indeed, we recently demonstrated that human eosinophils express gd TCR and showed its involvement in Colo-205 cell death induction (18). Another receptor shared between T cells and eosinophils, 2B4, a member of the CD2 family, has also been involved in the cytotoxic activity of eosinophils toward a B lymphoma cell line (21).…”

“…So far, a single study demonstrated the cytotoxic activity of eosinophils toward a B lymphoma cell line in vitro and the implication of 2B4 receptor, a member of the CD2 family, in antitumor responses of eosinophils (21). In a recent study, we showed that eosinophils express the CD3-gdTCR, a receptor shared with the gd T cells (18). These data suggesting tumoricidal properties of eosinophils led us to further investigate the molecular interactions of eosinophils with tumor cells using the Colo-205 colorectal tumor cell line as target cells.…”

“…Beside cytotoxic mediators, eosinophil granules contain multiple Th1, Th2, and immunoregulatory cytokines that are rapidly and selectively secreted (16). Among them, IFN, IFN-g, and TNF, which are known to play a major role during antitumor responses, are released by eosinophils (17,18). Some cellular interactions between eosinophils and tumor cells in situ have also been described (19,20).…”

IL-18 Is Involved in Eosinophil-Mediated Tumoricidal Activity against a Colon Carcinoma Cell Line by Upregulating LFA-1 and ICAM-1

“…TATE was considered an independent prognostic indicator; thus, increased eosinophil counts indicated increased survival (5,6). Recently, we (8,9) and other investigators (10) showed that human eosinophils expressed receptors and mediators, such as 2B4, TCRgd/ CD3 complex, and granzyme A, which were shared with lymphocytes and involved in antitumor defense. Eosinophil stimulation through these receptors induced tumor cell death in vitro.…”

Role of Il-5 and Eotaxin in Development of Blood Eosinophilic Reaction During Pulmonary Tuberculosis

“…В настоящем исследовании мы попыта-лись оценить способность эозинофильных гра-нулоцитов секретировать данный цитокин в ин-тактной культуре клеток и при добавлении в культуральную суспензию вакцинного штамма BCG (живой аттенуированный штамм M. bovis). Выбор индуктора, в частности, был обусловлен способностью лейкоцитов эозинофильного ряда непосредственно взаимодействовать с микобак-териями различных видов с последующим вы-свобождением широкого спектра цитокиновых молекул [13]. Как показали результаты прове-денных нами исследований, спонтанная и BCG-индуцированная секреция IL-5 эозинофильными гранулоцитами периферической крови оказалась достоверно выше у больных туберкулезом легких, сопровождающимся эозинофилией, по сравне-нию с аналогичными показателями у здоровых доноров и у пациентов с туберкулезной инфек-цией без эозинофилии (табл.…”