Arrest of human dendritic cells at the CD34-/CD4+/HLA-DR+ stage in the bone marrow of NOD/SCID-human chimeric mice

Nobuyoshi M, Kusunoki Y, Seyama T, Kodama K, Kimura A, Kyoizumi S
Blood 97(11):3655-7, 2001

Summary

Human dendritic cell (DC) precursors were engrafted and maintained in nonobese diabetic severe combined immunodeficient (NOD/SCID)-human chimeric mice (NOD/SCID-hu mice) transplanted with human cord blood mononuclear cell (CBMNC). However, no human mature DC was detected. Two months after implantation, mononuclear cells collected from the bone marrow (BM) of NOD/SCID-hu mice formed colonies of cells exhibiting DC morphology when cultured for one week with granulocyte macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha). In methylcellulose culture with GM-CSF and TNF-alpha, flow cytometric analysis showed the generation of CD1a⁺/CD14^– DC. Both CD4⁺/HLA-DR^hi (CD4⁺/DR^hi) and CD4⁺/HLA-DR^lo (CD4⁺/DR^lo ) cell fractions in NOD/SCID-hu mice BM exhibited DC morphology, CD1a expression, and high stimulating activity in mixed leukocyte reaction (MLR) after one week in both GM-CSF and TNF-alpha cultures. The surface phenotypes of the majority of both primary CD4⁺/DR^hi and CD4⁺/DR^lo cells were CD1a^–, CD11a⁺, CD34^–, and CD83^–, but 20 to 30% were CD11c⁺ and ten to 20% were CD14⁺. The most prominent differences were that the primary CD4⁺/DR^hi cell population highly expressed HLA-DQ and CD1a⁺/CD14^– cells were more frequently generated from CD4⁺/DR^hi cells than CD4⁺/DR^lo cells. This suggests that the CD4⁺/DR^hi fraction contains more DC precursors than CD4⁺/DR^lo.