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

ABSTRAC: Humanized NOD/SCID/IL-2 receptor γ-chainnull (huNSG) mice recapitulate some features of human T-cell po pulations 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 par ticularly 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.

• Autores: Perdomo Celis, Federico; Rugeles López, María Teresa; Zapata Jiménez, Juan Carlos; Taborda Vanegas, Natalia Andrea; Kottilil, Shyamasundaram; Bryant, Joseph; Medina Moreno, Sandra; Davis, Harry
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2020
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/36425
• Acceso en línea: https://hdl.handle.net/10495/36425
• Palabra clave: Receptores CXCR5; Receptors, CXCR5; Linfocitos T CD8-positivos; CD8-Positive T-Lymphocytes; Interleucina-23; Interleukin-23; Ratones Endogámicos; Mice, Inbred Strains; Infecciones por VIH; HIV Infections; Células Cultivadas; Cells, Cultured; Células Madre Hematopoyéticas; Hematopoietic Stem Cells
• Rights: openAccess
• License: http://creativecommons.org/licenses/by-nc-nd/2.5/co/