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Alpha Interferon and HIV Infection Cause Activation of Human T Cells in NSG-BLT Mice
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| Zeitschriftentitel: | Journal of Virology |
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| Personen und Körperschaften: | , |
| In: | Journal of Virology, 86, 2012, 6, S. 3327-3336 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society for Microbiology
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| Schlagwörter: |
| Zusammenfassung: | <jats:title>ABSTRACT</jats:title> <jats:p> The development of small animal models for the study of HIV transmission is important for evaluation of HIV prophylaxis and disease pathogenesis. In humanized bone marrow-liver-thymus (BLT) mice, hematopoiesis is reconstituted by implantation of human fetal liver and thymus tissue (Thy/Liv) plus intravenous injection of autologous liver-derived hematopoietic stem progenitor cells (HSPC). This results in reconstitution of human leukocytes in the mouse peripheral blood, lymphoid organs, and mucosal sites. NOD- <jats:italic>scid</jats:italic> interleukin-2 receptor-negative (IL-2Rγ <jats:sup>−/−</jats:sup> ) (NSG)-BLT mice were inoculated intravaginally with HIV and were monitored for plasma viremia by a branched DNA assay 4 weeks later. T-cell activation was determined by expression of CD38 and HLA-DR on human CD4 <jats:sup>+</jats:sup> and CD8 <jats:sup>+</jats:sup> T cells in mouse peripheral blood at the time of inoculation and 4 weeks later. Additional BLT mice were treated with human alpha interferon 2b (IFN-α2b) (intron A) and assessed for T-cell activation. Productive HIV infection in BLT mice was associated with T-cell activation (increases in CD38 mean fluorescence intensity and both the frequency and absolute number of CD38 <jats:sup>+</jats:sup> HLA-DR <jats:sup>+</jats:sup> T cells) that correlated strongly with plasma viral load and was most pronounced in the CD8 <jats:sup>+</jats:sup> T-cell compartment. This T-cell activation phenotype was recapitulated in NSG-BLT mice treated with intron A. HIV susceptibility correlated with the number of HSPC injected, yet a number of mice receiving the Thy/Liv implant alone, with no HSPC injection, were also susceptible to intravaginal HIV. These results are consistent with studies linking T-cell activation to progressive disease in humans and lend support for the use of NSG-BLT mice in studies of HIV pathogenesis. </jats:p> |
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| Umfang: | 3327-3336 |
| ISSN: |
0022-538X
1098-5514 |
| DOI: | 10.1128/jvi.06676-11 |