Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
PLoS One. 2010 Oct 1;5(10):e13109. doi: 10.1371/journal.pone.0013109.
Humanized mice, which are generated by transplanting human CD34+ hematopoietic stem cells into immunodeficient mice, are expected to be useful for the research on human immune responses. It is reported that antigen-specific T cell responses occur in immunodeficient mice transplanted with both human fetal thymus/liver tissues and CD34+ fetal cells, but it remains unclear whether antigen-specific T cell responses occur in those transplanted with only human CD34+ hematopoietic stem cells (HSCs). Here we investigated the differentiation and function of human CD8+ T cells reconstituted in NOD/SCID/Jak3⁻/⁻ mice transplanted with human CD34+ HSCs (hNOK mice). Multicolor flow cytometric analysis demonstrated that human CD8+ T cells generated from the CD34+ HSCs comprised only 3 subtypes, i.e., CD27(high)CD28+CD45RA+CCR7+, CD27+CD28+CD45RA⁻CCR7+, and CD27+CD28+CD45RA⁻CCR7⁻and had 3 phenotypes for 3 lytic molecules, i.e., perforin(Per)⁻granzymeA(GraA)⁻granzymeB(GraB)⁻, Per⁻GraA+GraB⁻, and Per(low)GraA+GraB+. These CD8+ T cells failed to produce IFN-γ and to proliferate after stimulation with alloantigens. These results indicate that the antigen-specific T cell response cannot be elicited in mice transplanted with only human CD34+ HSCs, because the T cells fail to develop normally in such mice.
人源化小鼠是通过将人 CD34+造血干细胞移植到免疫缺陷小鼠中而产生的，预计将有助于研究人类免疫反应。据报道，在移植了人胎胸腺/肝组织和 CD34+胎儿细胞的免疫缺陷小鼠中会发生抗原特异性 T 细胞反应，但尚不清楚在仅移植人 CD34+造血干细胞（HSCs）的小鼠中是否会发生抗原特异性 T 细胞反应。在这里，我们研究了在移植了人 CD34+HSCs（hNOK 小鼠）的 NOD/SCID/Jak3⁻/⁻小鼠中重建的人 CD8+T 细胞的分化和功能。多色流式细胞术分析表明，源自 CD34+HSCs 的人 CD8+T 细胞仅包含 3 种亚型，即 CD27(high)CD28+CD45RA+CCR7+、CD27+CD28+CD45RA⁻CCR7+和 CD27+CD28+CD45RA⁻CCR7⁻，并且具有 3 种用于 3 种裂解分子的表型，即穿孔素（Per）⁻颗粒酶 A（GraA）⁻颗粒酶 B（GraB）⁻、Per⁻GraA+GraB⁻和 Per(low)GraA+GraB+。这些 CD8+T 细胞在受到同种异体抗原刺激后无法产生 IFN-γ和增殖。这些结果表明，在仅移植人 CD34+HSCs 的小鼠中不能引发抗原特异性 T 细胞反应，因为 T 细胞在这些小鼠中无法正常发育。
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