التفاصيل البيبلوغرافية
| العنوان: |
NOD Facilitating Cells Exhibit Significantly Impaired Function. |
| المؤلفون: |
Yiming Huang, Fugier-Vivier, Isabelle J., Miller, Thomas, Elliott, Mary J., Tanner, Michael K., Atay, Safinur, Chilton, Paula M., Hong Xu, Ildstad, Suzanne T. |
| المصدر: |
Diabetes. Jun2007 Supplement 1, Vol. 56, pA520-A520. 1/4p. 1 Graph. |
| مصطلحات موضوعية: |
*CELLS, *BONE marrow, *HEMATOPOIETIC stem cells, *DENDRITIC cells, *MONOCYTES, *T cells, *LABORATORY mice |
| مستخلص: |
We previously reported that bone marrow-derived CD8[sup +]/TCR[sup -] grafting facilitating cells (FC) enhance hematopoietic stem cell (HSC) engraftment in allogeneic and syngeneic recipients and that B220[sup +]/CD11C[sup +]/CD11[sup -] precursor plasmacytoid dendritic cell (p-pre DC) FC subpopulation plays a critical and dominant role in facilitation. NOD mice exhibit a number of defects in innate and adaptive immunity including impaired myeloid differentiation and function in antigen presenting cell, NK cells, NKT cells and regulatory T cells. In the present studies, we evaluated the function of NOD FC. We reported for the first time that FC from NOD mice are functionally impaired in vivo and in vitro. CD8[sup +]/TCR[sup -] FC were sorted from NOD, NOR or B6 bone marrow and evaluated for subpopulations we previously found in B6 FC: NK FC, myeloid cells, CD19 FC, monocytes, and p-preDC. p-pre DC FC represented the major FC subpopulation in all strains examined. The CD 19[sup +] FC subpopulation was selectively significantly decreased in NOD FC compared to those from B6 or NOR mice (12% versus 26%, P <0.05). To test the function of NOD or NOR FC, 500 NOR HSC (c-Kit[sup +]/Sca-l[sup +]/Lin[sup -]) were sorted and transplanted with 30,000 NOR FC (n = 10) or without FC (n=16) into conditioned 950 cGy NOR recipients. The NOR FC significantly enhanced engraftment of NOR HSC compared to the HSC alone (p = 0.029) (Figure 1a). In striking contrast, NOD FC did not facilitate, as evidenced by the similar engraftment of HSC with NOD FC (n=13) compared to the NOD HSC alone (n=17; p = 0.579) (Figure lb). Impaired function of NOD FC was confirmed in vitro using colony forming cell (CFC) assay. NOD FC did not increase colony production when cultured with NOD HSC (Figure 1c), while NOR FC did (Figure ld). These results point without ambiguity to a defect in NOD FC that is not present in the NOR FC. Studies are underway to determine: (1) the mechanism of defective FC in NOD mice; (2) whether function of the FC can be restored in NOD mice with flt3-ligand treatment. [ABSTRACT FROM AUTHOR] |
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