γδ T cells confer protection against murine cytomegalovirus (MCMV).

Cytomegalovirus (CMV) is a leading infectious cause of morbidity in immune-compromised patients. γδ T cells have been involved in the response to CMV but their role in protection has not been firmly established and their dependency on other lymphocytes has not been addressed. Using C57BL/6 αß and/or γδ T cell-deficient mice, we here show that γδ T cells are as competent as αß T cells to protect mice from CMV-induced death. γδ T cell-mediated protection involved control of viral load and prevented organ damage. γδ T cell recovery by bone marrow transplant or adoptive transfer experiments rescued CD3ε-/- mice from CMV-induced death confirming the protective antiviral role of γδ T cells. As observed in humans, different γδ T cell subsets were induced upon CMV challenge, which differentiated into effector memory cells. This response was observed in the liver and lungs and implicated both CD27+ and CD27- γδ T cells. NK cells were the largely preponderant producers of IFNγ and cytotoxic granules throughout the infection, suggesting that the protective role of γδ T cells did not principally rely on either of these two functions. Finally, γδ T cells were strikingly sufficient to fully protect Rag-/-γc-/- mice from death, demonstrating that they can act in the absence of B and NK cells. Altogether our results uncover an autonomous protective antiviral function of γδ T cells, and open new perspectives for the characterization of a non classical mode of action which should foster the design of new γδ T cell based therapies, especially useful in αß T cell compromised patients.

Amaryllidaceae Alkaloids Decrease the Proliferation, Invasion, and Secretion of Clinically Relevant Cytokines by Cultured Human Colon Cancer Cells.

Alkaloids isolated from members of the Amaryllidaceae plant family are promising anticancer agents. The purpose of the current study was to determine if the isocarbostyrils narciclasine, pancratistatin, lycorane, lycorine, crinane, and haemanthamine inhibit phenomena related to cancer progression in vitro. To achieve this, we examined the proliferation, adhesion, and invasion of cultured human colon cancer cells via MTT assay and Matrigel-coated Boyden chambers. In addition, Luminex assays were used to quantify the secretion of matrix metalloproteinases (MMP) and cytokines associated with poor clinical outcomes. We found that all alkaloids decreased cell proliferation regardless of TP53 status, with narciclasine exhibiting the greatest potency. The effects on cell proliferation also appear to be specific to cancer cells. Narciclasine, lycorine, and haemanthamine decrease both adhesion and invasion but with various potencies depending on the cell line. In addition, narciclasine, lycorine, and haemanthamine decreased the secretion of MMP-1, -2, and -7, as well as the secretion of the cytokines pentraxin 3 and vascular endothelial growth factor. In conclusion, the present study shows that Amaryllidaceae alkaloids decrease phenomena and cytokines associated with colorectal cancer progression, supporting future investigations regarding their potential as multifaceted drug candidates.