Metallophilic macrophages are lacking in the thymus of lymphotoxin-beta receptor-deficient mice.

Institute of Histology and Embryology, University of Belgrade Medical School, Visegradska 26, 11000 Belgrade, Serbia and Montenegro.
Histochemie (Impact Factor: 2.93). 01/2007; 126(6):687-93. DOI: 10.1007/s00418-006-0202-5
Source: PubMed

ABSTRACT Lymphotoxin-beta receptor (LTbetaR) axis plays a crucial role in development and compartmentalization of peripheral lymphatic organs. But, it is also required for the appropriate function and maintenance of structural integrity of the thymus: in LTbetaR-deficient animals the clonal deletion of autoreactive lymphocytes is impaired and differentiation of thymic medullary epithelial cells is disturbed. In this study, using several markers, we showed that thymic metallophilic macrophages were lacking in LTbetaR-deficient mice. In tumor necrosis factor receptor-I (p55)-deficient mice (which we used as positive control) thymic metallophilic cells were located, similarly as in normal mice, in the thymic cortico-medullary zone at the junction of cortex and medulla. These findings show that LTbetaR is necessary for maintenance of metallophilic macrophages in the thymus and provide further evidence that these cells may represent a factor involved in thymic negative selection.

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: For a very long time, we studied the metallophilic macrophages of the rodent thymus and in this review our results on morphological, histochemical, enzymehistochemical, immunohistochemical, ultrastructural and functional features of these cells, as well as the molecular regulation of their development, will be presented. Furthermore, the differences between species will also be discussed and the comparisons with similar/related cell types (metallophilic macrophages in the marginal sinus of the spleen, subcapsular sinus of the lymph nodes and germinal centers of secondary lymphoid follicles) will be made. Metallophilic macrophages are strategically positioned in the thymic cortico-medullary zone and are very likely to be involved in: (i) the metabolism, synthesis and production of bioactive lipids, most likely arachidonic acid metabolites, based on their histochemical and enzymehistochemical features, and (ii) the process of negative selection that occurs in the thymus, based on their ultrastructural features and their reactivity after the application of toxic or immunosuppressive/immunomodulatory agents. Taken together, their phenotypic and functional features strongly suggest that metallophilic macrophages play a significant role in the thymic physiology.
    Progress in Histochemistry and Cytochemistry 01/2013; · 5.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Studies published in Histochemistry and Cell Biology in the year 2011 represent once more a manifest of established and newly sophisticated techniques being exploited to put tissue- and cell type-specific molecules into a functional context. The review is therefore the Histochemistry and Cell Biology's yearly intention to provide interested readers appropriate summaries of investigations touching the areas of tissue biology, developmental biology, the biology of the immune system, stem cell research, the biology of subcellular compartments, in order to put the message of such studies into natural scientific-/human- and also pathological-relevant correlations.
    Histochemie 02/2012; 137(4):403-57. · 2.93 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Extrathymic CD4+CD8+ double-positive (DP) T cells are increased in some pathophysiological conditions, including infectious diseases. In the murine model of Chagas disease, it has been shown that the protozoan parasite Trypanosoma cruzi is able to target the thymus and induce alterations of the thymic microenvironment and the lymphoid compartment. In the acute phase, this results in a severe atrophy of the organ and early release of DP cells into the periphery. To date, the effect of the changes promoted by the parasite infection on thymic central tolerance has remained elusive. Herein we show that the intrathymic key elements that are necessary to promote the negative selection of thymocytes undergoing maturation during the thymopoiesis remains functional during the acute chagasic thymic atrophy. Intrathymic expression of the autoimmune regulator factor (Aire) and tissue-restricted antigen (TRA) genes is normal. In addition, the expression of the proapoptotic Bim protein in thymocytes was not changed, revealing that the parasite infection-induced thymus atrophy has no effect on these marker genes necessary to promote clonal deletion of T cells. In a chicken egg ovalbumin (OVA)-specific T-cell receptor (TCR) transgenic system, the administration of OVA peptide into infected mice with thymic atrophy promoted OVA-specific thymocyte apoptosis, further indicating normal negative selection process during the infection. Yet, although the intrathymic checkpoints necessary for thymic negative selection are present in the acute phase of Chagas disease, we found that the DP cells released into the periphery acquire an activated phenotype similar to what is described for activated effector or memory single-positive T cells. Most interestingly, we also demonstrate that increased percentages of peripheral blood subset of DP cells exhibiting an activated HLA-DR+ phenotype are associated with severe cardiac forms of human chronic Chagas disease. These cells may contribute to the immunopathological events seen in the Chagas disease.
    PLoS Neglected Tropical Diseases 08/2011; 5(8):e1268. · 4.49 Impact Factor