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. (21st January 2020)

• Record Type: Journal Article
• Authors: Perdomo‐Celis, F.; Medina‐Moreno, S.; Davis, H.; Bryant, J.; Taborda, N. A.; Rugeles, M. T.; Kottilil, S.; Zapata, J. C.
• Is Part Of: Clinical and experimental immunology. Volume 200:Number 2(2020)
• Page Start: 185
• Page End: 198
• Publication Date: 2020-01-21
• Subjects: CD38 -- HIV -- HLA‐DR -- IL‐17A -- NSG‐SGM3 -- PD‐1 -- T cell; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.13416
• Languages: English
• ISSNs: 0009-9104

Abstract

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