Abstract
Mixed allogeneic chimeras are emerging as a prospective approach to induce immune tolerance in clinics. However, the immunological function of macrophages in mixed chimeras has not been evaluated. Using a B6→BALB/c mixed chimera model, we investigated the phenotype and function of F4/80+ resident peritoneal exudate macrophage (PEMs) and splenic macrophages (SPMs) in vitro and in vivo. Recipient F4/80+PEMs and SPMs in mixed chimeras expressed significantly lower levels of MHC-II, CD54, and CD23 than those in non-chimeric mice before lipopolysaccharide stimulation. Recipient F4/80+PEMs and SPMs in mixed chimeras induced normal cell proliferation and delayed-type hypersensitivity of allo-T cells, but they induced more IFN-γ and IL-2 products and less IL-10 and TGF-β products of allo-T cells compared with those of non-chimeras. Furthermore, recipient F4/80+PEMs and SPMs had significantly higher phagocytotic capacity against chicken red blood cells or allo-T cells than those of controls while they had normal phagocytosis to Escherichia coli. Although some slight but significant alterations of recipient macrophages have been detected, these results provide direct evidences for the efficient immunity of recipient macrophages in mixed allogeneic chimeras. The present study also, for the first time, offered basic information for macrophages maturing in heterogeneous environments.
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Abbreviations
- APCs:
-
antigen-presenting cells
- CFSE:
-
5-(and-6)-carboxyfluorescein diacetate succinimidyl ester
- cRBC:
-
chicken red blood cells
- DTH:
-
delayed-type hypersensitivity
- E. coli:
-
Escherichia coli
- FCM:
-
flow cytometry
- IFN-γ:
-
interferon-γ
- IL-10:
-
interleukin-10
- LPS:
-
lipopolysaccharide
- MFI:
-
median fluorescence intensity
- MLR:
-
mixed leukocyte reactions
- NO:
-
nitric oxide
- PEMs:
-
peritoneal exudate macrophages
- SPMs:
-
splenic macrophages
- TBI:
-
total body irradiation
- TPM:
-
two photon microscope
- TGF-β1:
-
transforming growth factor-β1
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Acknowledgments
The authors wish to thank Mr. Aqeel Javeed for his kind review of the manuscript, Ms. Jing Wang, Mr. Chunsheng Zhang and Mr. Yabing Liu for their expert technical assistance, Ms. Qinghuan Li, for her excellent laboratory management, and Ms. Yuli Liu for her outstanding animal husbandry. This work was supported by grants from the National Natural Science Foundation (NNSF) for Young Scientists (No.30600567, G.L.), the NNSF for Key Programs (No. 30630060, Y.Z.), the NNSF for Distinguished Young Scholars (No. 30425026, Y.Z.), the Knowledge Innovation Program of CAS (KSCX2-SW-333, Y.Z.), the National Basic Research Program (973 Program, 2003CB515501, Y.Z.), 100 Quality Vocational Colleagues of the CAS (2003-85, Y.Z.), and the Scientific Research Foundation for Returned Overseas Chinese Scholars, State Education Ministry (2005-546, Y.Z.).
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Liu, G., Ma, H., Jiang, L. et al. The immunity of splenic and peritoneal F4/80+ resident macrophages in mouse mixed allogeneic chimeras. J Mol Med 85, 1125–1135 (2007). https://doi.org/10.1007/s00109-007-0215-0
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DOI: https://doi.org/10.1007/s00109-007-0215-0