| Author | Espíndola, Otávio de Melo | |
| Author | Rijnstra, Esther Siteur-van | |
| Author | Frankin, Esmay | |
| Author | Weijer, Kees | |
| Author | Velden, Yme Ubeles van der | |
| Author | Berkhout, Ben | |
| Author | Blom, Bianca | |
| Author | Villaudy, Julien | |
| Access date | 2021-11-04T23:18:11Z | |
| Available date | 2021-11-04T23:18:11Z | |
| Document date | 2021 | |
| Citation | ESPÍNDOLA, Otávio de Melo et al. Early Effects of HTLV-1 Infection on the Activation, Exhaustion, and Differentiation of T-Cells in Humanized NSG Mice. Cells, v. 10, n. 10, p. 1-17, Sep. 2021. | pt_BR |
| ISSN | 2073-4409 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/49690 | |
| Language | eng | pt_BR |
| Publisher | MDPI | pt_BR |
| Rights | open access | pt_BR |
| Title | Early Effects of HTLV-1 Infection on the Activation, Exhaustion, and Differentiation of T-Cells in Humanized NSG Mice | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.3390/cells10102514 | |
| Abstract | Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy of CD4+ T-cells associated with HTLV-1 infection. In this study, we used the model of immunodeficient NSG mice reconstituted with a functional human immune system (HIS) to investigate early events in HTLV-1 pathogenesis. Upon infection, human T-cells rapidly increased in the blood and lymphoid tissues, particularly CD4+CD25+ T-cells. Proliferation of CD4+ T-cells in the spleen and mesenteric lymph nodes (MLN) correlated with HTLV-1 proviral load and CD25 expression. In addition, splenomegaly, a common feature of ATLL in humans, was also observed. CD4+ and CD8+ T-cells predominantly displayed an effector memory phenotype (CD45RA-CCR7-) and expressed CXCR3 and CCR5 chemokine receptors, suggesting the polarization into a Th1 phenotype. Activated CD8+ T-cells expressed granzyme B and perforin; however, the interferon-γ response by these cells was limited, possibly due to elevated PD-1 expression and increased frequency of CD4+FoxP3+ regulatory T-cells in MLN. Thus, HTLV-1-infected HIS-NSG mice reproduced several characteristics of infection in humans, and it may be helpful to investigate ATLL-related events and to perform preclinical studies. Moreover, aspects of chronic infection were already present at early stages in this experimental model. Collectively, we suggest that HTLV-1 infection modulates host immune responses to favor viral persistence. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Neuroinfecções. Rio de Janeiro, RJ, Brasil / University of Amsterdam. Location AMC. Amsterdam University Medical Centers. Department of Experimental Immunology. Amsterdam, The Netherlands. | pt_BR |
| Affilliation | University of Amsterdam. Location AMC. Amsterdam University Medical Centers. Department of Experimental Immunology. Amsterdam, The Netherlands. | pt_BR |
| Affilliation | University of Amsterdam. Location AMC. Amsterdam University Medical Centers. Department of Experimental Immunology. Amsterdam, The Netherlands. | pt_BR |
| Affilliation | University of Amsterdam. Location AMC. Amsterdam University Medical Centers. Department of Experimental Immunology. Amsterdam, The Netherlands. | pt_BR |
| Affilliation | University of Amsterdam. Location AMC. Amsterdam University Medical Centers. Department of Experimental Immunology. Laboratory of Experimental Virology. Amsterdam, The Netherlands. | pt_BR |
| Affilliation | University of Amsterdam. Location AMC. Amsterdam University Medical Centers. Department of Experimental Immunology. Laboratory of Experimental Virology. Amsterdam, The Netherlands. | pt_BR |
| Affilliation | University of Amsterdam. Location AMC. Amsterdam University Medical Centers. Department of Experimental Immunology. Amsterdam, The Netherlands. | pt_BR |
| Affilliation | University of Amsterdam. Location AMC. Amsterdam University Medical Centers. Department of Experimental Immunology. Laboratory of Experimental Virology. Amsterdam, The Netherlands / J&S Preclinical Solutions. The Netherlands. | pt_BR |
| Subject | ATLL | pt_BR |
| Subject | HTLV-1 | pt_BR |
| Subject | NSG mice | pt_BR |
| Subject | T-cells | pt_BR |
| Subject | Chemokine receptors | pt_BR |
| Subject | Exhaustion | pt_BR |
| Subject | Humanized mice | pt_BR |
