期刊
EXPERIMENTAL HEMATOLOGY
卷 36, 期 4, 页码 464-472出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.exphem.2007.12.010
关键词
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资金
- NCI NIH HHS [CA84156, R21 CA089567-02, CA89567, R01 CA084156, R21 CA089567-01] Funding Source: Medline
- NIAID NIH HHS [AI42955] Funding Source: Medline
- NIDDK NIH HHS [R01 DK066917-04, R01 DK066917-03, DK66917, R01 DK066917-01, R01 DK066917, R01 DK066917-02] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R21CA089567, R01CA084156] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R21AI042955, R01AI042955] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK066917] Funding Source: NIH RePORTER
Objective. Bone marrow (BM) Th1 populations can contribute to graft-vs-leukemia responses. Granulocyte/granulocyte macrophage colony-stimulating factor (CSF)-mobilized peripheral blood progenitor cells (PBPC) have become widely accepted alternatives to BM transplantation. T cells coexpressing natural killer cell proteins (NKT) include a CD1d-reactive subset that influences immunity by rapidly producing large amounts of Th1 and/or Th2 cytokines dependent upon microenvironment and disease. There are two types of CD1d-reactive NKT. iNKT express a semi-invariant T-cell receptor-alpha. Other noninvariant CD1d-reactive NKT from BM and liver produce large amounts of interleukin-4 or interferon-gamma, respectively, and within the intestine can be biased in either direction. Recent data suggests that NKT might contribute to clinical benefits of PBPC. Materials and Methods. To address these issues, we phenotypically and functionally studied PBPC NKT. Results. Similarly to BM, NKT-like cells were common in allogeneic and autologous PBPC, there were relatively few classical iNKT, but high CD1d-reactivity concentrated in NKT fractions. Significantly, PBPC CD1d-reactive cells were relatively Th1-biased and their presence was associated with better prognosis. Granulocyte CSF treatment of BM to yield PBPC in vivo as well as in vitro Th2-polarizes conventional T cells and iNKT. However, granulocyte CSF treatment of BM in vitro produced Th1-biased NKT, providing a mechanism for opposite polarization of NKT from BM vs PBPC. Conclusions. These results suggest distinct Th1 CD1d-reactive NKT cells could stimulate anti-tumor responses from those previously described, which can suppress graft-vs-host disease. (C) 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
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