Effective elicitation of human effector CD8+ T Cells in HLA-B*51:01 transgenic humanized mice after infection with HIV-1.
Humanized mice are expected to be useful as small animal models for in vivo studies on the pathogenesis of infectious diseases. However, it is well known that human CD8(+) T cells cannot differentiate into effector cells in immunodeficient mice transplanted with only human CD34(+) hematopoietic stem...
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| Autores principales: | , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2012
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/5f7987c01ea04749a1b522c3e384b866 |
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| Sumario: | Humanized mice are expected to be useful as small animal models for in vivo studies on the pathogenesis of infectious diseases. However, it is well known that human CD8(+) T cells cannot differentiate into effector cells in immunodeficient mice transplanted with only human CD34(+) hematopoietic stem cells (HSCs), because human T cells are not educated by HLA in the mouse thymus. We here established HLA-B*51:01 transgenic humanized mice by transplanting human CD34(+) HSCs into HLA-B*51:01 transgenic NOD/SCID/Jak3(-/-) mice (hNOK/B51Tg mice) and investigated whether human effector CD8(+) T cells would be elicited in the mice or in those infected with HIV-1 NL4-3. There were no differences in the frequency of late effector memory and effector subsets (CD27(low)CD28(-)CD45RA(+/-)CCR7(-) and CD27(-)CD28(-)CD45RA(+/-)CCR7(-), respectively) among human CD8(+) T cells and in that of human CD8(+) T cells expressing CX3CR1 and/or CXCR1 between hNOK/B51Tg and hNOK mice. In contrast, the frequency of late effector memory and effector CD8(+) T cell subsets and of those expressing CX3CR1 and/or CXCR1 was significantly higher in HIV-1-infected hNOK/B51Tg mice than in uninfected ones, whereas there was no difference in that of these subsets between HIV-1-infected and uninfected hNOK mice. These results suggest that hNOK/B51Tg mice had CD8(+) T cells that were capable of differentiating into effector T cells after viral antigen stimulation and had a greater ability to elicit effector CD8(+) T cells than hNOK ones. |
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