Characterization of CXCR5 + CD8 + T-cells in humanized NSG mice.

Humanized NOD/SCID/IL-2 receptor γ-chain ^null (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. Published by Elsevier GmbH.. All rights reserved.)