title: Effective elicitation of human effector CD8+ T Cells in HLA-B*51:01 transgenic humanized mice after infection with HIV-1.
abstract: 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.
authors.affiliation: Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Sato
authors.forename: Sayaka
authors.initials: S
authors.lastname: Nagata
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takiguchi
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000073883:CX3C Chemokine Receptor 1; D004195:Disease Models, Animal; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D059949:HLA-B51 Antigen / Q000276:immunology*; D006801:Humans; D053616:Janus Kinase 3 / Q000172:deficiency / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D010641:Phenotype; D019707:Receptors, Chemokine / Q000276:immunology; D023062:Receptors, Interleukin-8A / Q000276:immunology
chemical_list: D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D059949:HLA-B51 Antigen; D019707:Receptors, Chemokine; D023062:Receptors, Interleukin-8A; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3