High activation and skewed T‐cell differentiation are associated with low IL‐17A levels in a hu‐PBL‐NSG‐SGM3 mouse model of HIV infection

作者: F. Perdomo‐Celis , S. Medina‐Moreno , H. Davis , J. Bryant , N. A. Taborda

DOI: 10.1111/CEI.13416

关键词: ImmunologyCD8CD38Immune systemInterleukinStem cell factorT cellHLA-DRHuman leukocyte antigenBiology

摘要: The humanized NOD/SCID/IL-2 receptor γ-chainnull (NSG) mouse model has been widely used for the study of HIV pathogenesis. Here, NSG mice with transgenic expression human stem cell factor (SCF), granulocyte-macrophage colony-stimulating (GM-CSF) and interleukin (IL)-3 (NSG-SGM3) were injected peripheral blood leukocytes (PBL mice) from two HIV-infected (HIV+ ) patients who under anti-retroviral therapy (ART; referred as HIV+ or one HIV-seronegative healthy volunteer (HIV- ). Such are either hu-PBL-NSG-SGM3 HIV- mice, depending on source PBL. kinetics replication T responses following engraftment evaluated in secondary lymphoid tissues. High low CD4 : CD8 ratios observed absence (ART). Consistent high activation skewed differentiation cells donor, exhibited a higher co-expression leukocyte antigen D-related (HLA-DR) CD38 than well shifted to CCR7- CD45RA+ terminal effector profile, even presence ART. In addition, activation/differentiation disturbances associated decreased plasma levels IL-17A. Thus, this recapitulates some immune occurring patients, underlying its potential use studying pathogenic events during infection.

参考文章(66)
Ushani Srenathan, Kathryn Steel, Leonie S. Taams, IL-17+ CD8+ T cells: Differentiation, phenotype and role in inflammatory disease. Immunology Letters. ,vol. 178, pp. 20- 26 ,(2016) , 10.1016/J.IMLET.2016.05.001
N. Misawa, Y. Koyanagi, Y. Ueyama, M. Miyasaka, Y. Kawano, N. Yamamoto, Y. Tanaka, T. Tanaka, R. Tanaka, M. Ito, High levels of viremia in hu-PBL-NOD-scid mice with HIV-1 infection. Leukemia. ,vol. 11, pp. 109- 112 ,(1997)
Matthias Hoffmann, Nikos Pantazis, Genevieve E. Martin, Stephen Hickling, Jacob Hurst, Jodi Meyerowitz, Christian B. Willberg, Nicola Robinson, Helen Brown, Martin Fisher, Sabine Kinloch, Abdel Babiker, Jonathan Weber, Nneka Nwokolo, Julie Fox, Sarah Fidler, Rodney Phillips, John Frater, , Exhaustion of Activated CD8 T Cells Predicts Disease Progression in Primary HIV-1 Infection PLOS Pathogens. ,vol. 12, pp. e1005661- ,(2016) , 10.1371/JOURNAL.PPAT.1005661
Byung-Seok Kim, Young-Jun Park, Yeonseok Chung, Targeting IL-17 in autoimmunity and inflammation. Archives of Pharmacal Research. ,vol. 39, pp. 1537- 1547 ,(2016) , 10.1007/S12272-016-0823-8
Jessica R. Spengler, Kerry J. Lavender, Cynthia Martellaro, Aaron Carmody, Andreas Kurth, James G. Keck, Greg Saturday, Dana P. Scott, Stuart T. Nichol, Kim J. Hasenkrug, Christina F. Spiropoulou, Heinz Feldmann, Joseph Prescott, Ebola Virus Replication and Disease Without Immunopathology in Mice Expressing Transgenes to Support Human Myeloid and Lymphoid Cell Engraftment The Journal of Infectious Diseases. ,vol. 214, ,(2016) , 10.1093/INFDIS/JIW248
Joseph C. Mudd, Jason M. Brenchley, Gut Mucosal Barrier Dysfunction, Microbial Dysbiosis, and Their Role in HIV-1 Disease Progression. The Journal of Infectious Diseases. ,vol. 214, ,(2016) , 10.1093/INFDIS/JIW258
Collin Kieffer, Mark S Ladinsky, Allen Ninh, Rachel P Galimidi, Pamela J Bjorkman, Longitudinal imaging of HIV-1 spread in humanized mice with parallel 3D immunofluorescence and electron tomography eLife. ,vol. 6, ,(2017) , 10.7554/ELIFE.23282
Marc Veldhoen, Interleukin 17 is a chief orchestrator of immunity Nature Immunology. ,vol. 18, pp. 612- 621 ,(2017) , 10.1038/NI.3742
Sandra Medina-Moreno, Thomas C. Dowling, Juan C. Zapata, Nhut M. Le, Edward Sausville, Joseph Bryant, Robert R. Redfield, Alonso Heredia, Targeting of CDK9 with indirubin 3’-monoxime safely and durably reduces HIV viremia in chronically infected humanized mice PLOS ONE. ,vol. 12, pp. e0183425- ,(2017) , 10.1371/JOURNAL.PONE.0183425
Jessica R Spengler, Greg Saturday, Kerry J Lavender, Cynthia Martellaro, James G Keck, Stuart T Nichol, Christina F Spiropoulou, Heinz Feldmann, Joseph Prescott, Severity of Disease in Humanized Mice Infected With Ebola Virus or Reston Virus Is Associated With Magnitude of Early Viral Replication in Liver. The Journal of Infectious Diseases. ,vol. 217, pp. 58- 63 ,(2018) , 10.1093/INFDIS/JIX562