Another powerful animal model, particularly to study pathogens that are only tropic to primates,
are macaques. James Frencher from Zheng Chen’s lab (Chicago, IL, USA) showed evidence for HMB-PP-driven expansion of Vγ9/Vδ2 T cells in macaques infected with Listeria mono-cytogenes, and for priming of anti-microbial Th17 and Th22 responses by HMB-PP-responsive Vγ9/Vδ2 T cells Vorinostat price [15]. Leo Lefrançois (Farmington, CT, USA) presented new data suggesting a memory-like γδ T-cell response to oral Listeria infection in mice. Strikingly, this response is specific to an oligoclonal Vγ6/Vδ1 T-cell population present in mesenteric lymph nodes and lamina propria, which expand more rapidly and robustly to a secondary infection by Listeria but not to an unrelated pathogen, like Salmonella. γδ T cells are highly cytolytic against tumour cells, which has led to clinical trials based on their endogenous activation or adoptive transfer MK-2206 solubility dmso in/ to cancer patients [16]. Telma Lança from Bruno Silva-Santos’s lab (Lisboa, Portugal) stressed the importance of understanding the migratory properties of γδ T cells towards tumours. She showed that both mouse and human γδ T cells migrate in response to CCL2/CCR2 signals, and that these are required for the
in vivo infiltration of murine γδ T cells into tumour lesions. Using the B16 melanoma model, she further showed that mice genetically deficient for either γδ T cells (Trcd−/−) or CCR2 (Ccr2−/−) develop larger tumours (and more rapidly) than controls. Candida Vitale from Massimo Massaia’s lab (Torino, Italy) showed that cells from high-risk chronic SB-3CT lymphocytic leukaemia (CLL) patients with an unmutated tumour immunoglobulin heavy chain variable region
have an accelerated activity of the mevalonate pathway, thereby chronically stimulating peripheral Vγ9/Vδ2 T cells in those patients and driving their differentiation toward terminally differentiated, dysfunctional TEMRA cells, as opposed to patients with low-risk mutated CLL. TEMRA accumulation concurred to non-responsiveness to zoledronate in vitro which was an independent predictor of shorter time to first treatment (TTFT) in the overall patient cohort [17]. John Anderson (London, UK) presented evidence that human Vγ9/Vδ2 T cells effectively kill antibody-opsonised target cells through CD16-dependent antibody-dependent cell-mediated cytotoxicity (ADCC) and that the CD16 interaction is a requirement for the uptake of soluble material by Vγ9/Vδ2 T cells for presentation to antigen-specific CD8+ responder T cells.