A functional gammadeltaTCR/CD3 complex distinct from gammadeltaT cells is expressed by human eosinophils.

Abstract

BACKGROUND:Eosinophils are effector cells during parasitic infections and allergic responses. However, their contribution to innate immunity has been only recently unravelled. METHODOLOGY/PRINCIPAL FINDINGS:Here we show that human eosinophils express CD3 and gammadelta T Cell Receptor (TCR) but not alphabeta TCR. Surface expression of gammadeltaTCR/CD3 is heterogeneous between eosinophil donors and inducible by mycobacterial ligands. Surface immunoprecipitation revealed expression of the full gammadeltaTCR/CD3 complex. Real-time PCR amplification for CD3, gamma and delta TCR constant regions transcripts showed a significantly lower expression in eosinophils than in gammadeltaT 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-gamma and TNF-alpha) was observed following activation by gammadeltaTCR-specific agonists or by mycobacteria. These effects were inhibited by anti-gammadeltaTCR blocking antibodies and antagonists. Moreover, gammadeltaTCR/CD3 was involved in eosinophil cytotoxicity against tumor cells. CONCLUSIONS/SIGNIFICANCE:Our results provide evidence that human eosinophils express a functional gammadeltaTCR/CD3 with similar, but not identical, characteristics to gammadeltaTCR from gammadeltaT 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.