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 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^lowCD28^-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.