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AbstractHumanized NOD/SCID/IL-2 receptor γ-chainnull (huNSG) mice recapitulate some features of human T-cell populations that can be exploited in basic and pre-clinical research. CXCR5+ T CD8+ T-cells play an important role in the control of viral infections and tumors. Indeed, they have been associated with low-level HIV replication, making them a possible novel correlate of protection, and potentially useful in the eradication of HIV reservoirs. Here, by flow cytometry, we evaluated the reconstitution of CXCR5+ CD8+ T-cells in huNSG mice engrafted with CD34+ hematopoietic stem cells. This population was readily generated in huNSG mice, and where particularly confined to spleen and lymph nodes. These cells exhibited a follicular-like phenotype, with expression of Programmed Death (PD)-1, Inducible T-cell costimulatory (ICOS), and absence of CCR7. Moreover, CXCR5+ CD8+ T-cells had a higher expression of interleukin (IL)-21 and a higher cytotoxic potential compared with CXCR5− cells. HIV infection did not affect the frequencies of CXCR5+ CD8+ T-cells in secondary lymphoid organs. Finally, taking advantage of the high proportion of naïve T-cells in huNSG mice, we evaluated the in vitro response of splenic T-cells to the follicular profile-polarizing cytokines Transforming Growth Factor (TGF)-β1 and IL-23. After in vitro treatment, there was an increase in CXCR5+ CD8+ T-cells, which exhibited high levels of PD-1, CD40 L and low expression of CCR7. Thus, there is a reconstitution of CXCR5+ CD8+ T-cells in huNSG mice, supporting the use of this model for exploring the biology and role of this cell population in healthy and diseased conditions. Copyright 2019 The Authors
SponsorsThis work was supported by internal funds of the Institute of Human Virology of the University of Maryland School of Medicine Baltimore, USA.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85076253403&doi=10.1016%2fj.imbio.2019.11.020&partnerID=40&md5=8bad0fd0d7191d87951fedffc91a92b6; http://hdl.handle.net/10713/11545