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.
Highlights
Eosinophils are polymorphonuclear granulocytes mainly found in increased numbers during helminth parasitic infections and allergic reactions [1,2]
While lymphocytes from PBMC fraction expressed these markers at the expected frequencies (Figure 1B) and unlike a previous report [34], we were unable to detect CD3 or abTCR expression in neutrophils (Figure 1C)
As previously observed for other receptors such as CD25 [42], CD4 [18], FceRI, CD89 and CD28 [10], cdTCR/CD3 surface expression on eosinophils is highly heterogeneous between individual donors
Summary
Eosinophils are polymorphonuclear granulocytes mainly found in increased numbers during helminth parasitic infections and allergic reactions [1,2] They are classically considered as mediator-releasing cells during effector phase of adaptive immunity, under the influence of T cell dependent cytokines or chemokines and antibodies [2], whereas eosinophil-derived chemokines have been recently shown to locally attract Th2 lymphocytes at lung inflammatory sites [3,4]. Eosinophils are foremost present in mucosal tissues in contact with the environment such as in gastro-intestinal tract and skin [2] and are characterized by their wide morphological and functional heterogeneity [9] In addition to these effector functions, eosinophils produce several Th1, Th2 and regulatory cytokines, such as IL-10 [10,11], which, in contrast to T cells, are stored within granules and promptly released upon activation [12]. Their contribution to innate immunity has been only recently unravelled
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