Failure of effector function of human CD8+ T Cells in NOD/SCID/JAK3?/? immunodeficient mice transplanted with human CD34+ hematopoietic stem cells.

ABSTRACT: 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-? 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.

SUBMITTER: Sato Y 

PROVIDER: S-EPMC2948507 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature