ABSTRACT
Mouse peritoneal macrophages consist of two subsets: large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs), defined as CD11bhiF4/80hi and CD11b+F4/80lo cells, respectively. We reveal that SPMs, but not LPMs, have the ability to present antigens to naïve CD4+ T cells. Coculture of SPMs with naïve ovalbumin (OVA) specific CD4+ T cells (OT-II) in the presence of OVA peptide effectively induced CD4+ T cells priming. SPMs, but not LPMs, strongly express DNAM-1, an activating immunoreceptor. Although antigen uptake and processing were comparable between WT and DNAM-1-deficient SPMs, deficiency of DNAM-1 on SPMs or blockade of DNAM-1 and its ligand interaction impaired CD4+ T cells priming by SPMs. Furthermore, T and B cell responses in mediastinal lymph nodes of mice intraperitoneally immunized with trinitrophenyl (TNP)-OVA protein in Alum adjuvant were enhanced by intraperitoneally transferred wild-type, but not DNAM-1-deficient, SPMs. We propose that SPMs are functionally distinct from LPMs, and DNAM-1 plays a costimulatory role in antigen presentation by SPMs.
Subject(s)
Antigens, Differentiation, T-Lymphocyte/metabolism , CD4-Positive T-Lymphocytes/immunology , Cell Size , Lymphocyte Activation , Macrophages, Peritoneal/cytology , Macrophages, Peritoneal/metabolism , Animals , Antigens/immunology , Cell Proliferation , Cross-Priming/immunology , Germinal Center/metabolism , Immunization , Lymph Nodes/metabolism , Mediastinum/physiology , Mice, Inbred C57BL , Receptors, Virus/metabolismABSTRACT
DNAM-1 is an activating receptor expressed on NK cells and T cells and plays an important role in cytotoxicity of these cells against target cells. Although the role of DNAM-1 in the function of T cells and NK cells has been well studied, the expression and function of DNAM-1 on myeloid cells have been incompletely understood. In this study, we investigated expression of DNAM-1 on monocyte subsets in mouse peripheral blood and found that only inflammatory monocytes (iMos), but not patrolling monocytes (pMos), expressed high levels of DNAM-1. In addition, we found that DNAM-1 was highly expressed on iMos, rather than pMos, also in human. Furthermore, we found that DNAM-1 on inflammatory monocytes was involved in cell adhesion to CD155-expressing cells. Therefore, we propose that expression of DNAM-1 on inflammatory monocytes are evolutionally conserved and act as an adhesion molecule on blood inflammatory monocytes.
Subject(s)
Antigens, Differentiation, T-Lymphocyte/biosynthesis , Cell Adhesion Molecules/biosynthesis , Cell Adhesion/immunology , Inflammation/immunology , Monocytes/immunology , Animals , Antigens, Differentiation, T-Lymphocyte/immunology , Cell Adhesion Molecules/immunology , Flow Cytometry , Humans , Mice , Mice, Inbred C57BL , Mice, KnockoutABSTRACT
Acute graft-versus-host disease (GVHD) is a life-threatening complication following bone marrow transplantation; however, no effective molecular-targeting therapy has been determined. Here, we show that mice that received allogeneic splenocytes deficient in DNAX accessory molecule-1 (DNAM-1) had significantly milder GVHD and lower mortality than those that received allogeneic WT splenocytes. Donor CD8(+) T cells deficient in DNAM-1 showed significantly less proliferation and infiltration of the liver and intestines of recipient mice and produced less IFN-γ after coculture with allogeneic splenocytes than WT CD8(+) T cells. Mice prophylactically treated with an anti-DNAM-1 antibody showed milder GVHD and lower mortality than those treated with a control antibody. Moreover, treatment with a single administration of the antibody after the overt onset of GVHD ameliorated GVHD and prolonged survival. Finally, we show that the anti-DNAM-1 antibody therapy also ameliorated the overt GVHD in lethally irradiated mice after MHC-matched, minor antigen-mismatched bone marrow transplantation. These results indicate that DNAM-1 plays an important role in the development of GVHD and is an ideal molecular target for therapeutic approaches to GVHD.
Subject(s)
Antigens, Differentiation, T-Lymphocyte/immunology , Graft vs Host Disease/etiology , Graft vs Host Disease/immunology , Acute Disease , Animals , Antibodies, Monoclonal/therapeutic use , Antigens, Differentiation, T-Lymphocyte/genetics , Bone Marrow Transplantation/adverse effects , Bone Marrow Transplantation/immunology , Bone Marrow Transplantation/pathology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/pathology , Cell Proliferation , Female , Graft vs Host Disease/pathology , Graft vs Host Disease/therapy , Interferon-gamma/biosynthesis , Ligands , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Knockout , Transplantation, HomologousABSTRACT
We fabricated a novel x-ray polarimeter with a transmission multilayer and measured its performance with synchrotron radiation. A self standing multilayer with seven Mo/Si bilayers was installed with an incident angle of 45 degrees in front of a back-illuminated CCD. The multilayer can be rotated around the normal direction of the CCD keeping an incident angle of 45 degrees. This polarimeter can be easily installed along the optical axis of x-ray optics. By using the CCD as a photon counting detector with a moderate energy resolution, the polarization of photons in a designed energy band can be measured along with the image. At high photon energies, where the multilayer is transparent, the polarimeter can be used for imaging and spectroscopic observations. We confirmed a modulation factor of 45% with 45% and 17% transmission for P- and S-polarization, respectively.
