Histiocyte and T-cell-rich B-cell lymphoma with Langhans giant cells.
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Tuberculosis is characterized by a tight interplay between Mycobacterium tuberculosis (M. tb) and host cells within granulomas. These cellular aggregates restrain M. tb spreading but do not kill all bacilli, which persist for years. A more detailed investigation of the interaction between M. tb and granuloma cells is needed to improve our understanding of this persistence and to explain the physiopathology of tuberculosis. In the present study, a recently developed in vitro human model of tuberculous granulomas has been used to analyse the modulation of granuloma cell differentiation by M. tb, in comparison to poorly virulent mycobacteria, which do not persist. It is reported that whilst all mycobacteria species induce granuloma formation, only M. tb triggers the differentiation of granuloma macrophages into very large multinucleated giant cells (MGCs) that are unable to mediate any bacterial uptake. This loss of function is not due to cell quiescence, as MGCs still display NADPH oxidase activity, but it correlates with decreased expression of phagocytosis receptors. This phenomenon is specific for the virulent species of M. tuberculosis complex, as poorly virulent species only induce the formation of small multinucleated cells (MCs) with conserved mycobacterial uptake ability, which never reach the MGC differentiation stage. The phenotype of MGCs thus strongly resembles mature dendritic cells with a loss of microbial uptake ability, despite conserved antigen presentation. In M. tb-induced granulomas, MGCs thus seem to be devoted to the destruction of bacilli that have been ingested in previous differentiation stages, ie in macrophages and MCs.
Microscopic analysis of the development of Langhans' giant cells in lymph nodes of hyperimmunized animals was performed. It seems that they originate from the primitive mesenchymal cells, arranged along the blood vessels especially along the capillaries.
Granulomas were induced in rats by subcutaneous implantation of pieces of Melinex plastic into the dorsum. The pieces of Melinex were removed at intervals varying from 16 h to 14 days, and the adherent cells were studied morphologically and quantitatively. Giant cell formation started about 32 h after implantation. The first giant cells to appear were of the Langhans type. Two days after implantation, most of the giant cells are still Langhans-type cells. A few giant cells of the foreign-body type and transition forms between the Langhans and foreign-body types are also present. From the third day on, the foreign-body type gradually becomes predominant. Independent of the duration of implantation, giant cells with 3, 4, or 5 nuclei are virtually without exception of the Langhans type. The higher the number of nuclei between 6 and 30, the more cells are of the foreign-body type. Giant cells with 30 or more nuclei are all foreign-body type. The findings are discussed in the light of current knowledge concerning giant cell formation. It is concluded that under the present experimental conditions, Langhans-type giant cells are the precursors of foreign-body-type giant cells.
Granulomas were induced in rats by subcutaneous implantation of pieces of Melinex plastic into the dorsum. The pieces of Melinex were removed at intervals varying from 16h to 14 days, and the adherent cells were studied morphologically and quantitatively. Giant cell formation started about 32h after implantation. The first giant cells to appear were of the Langerhans type. Two days after implantation, most of the giant cells are still Langhans-type cells. A few giant cells of the foreign-body type and transition forms between the Langhans and foreign-body types are also present. From the third day on, the foreign-body type gradually becomes predominant. Independent of the duration of implantation, giant cells with 3, 4, or 5 nuclei are virtually without exception of the Langhans type. The higher the number of nuclei between 6 and 30, the more cells are of the foreign-body type. Giant cells with 30 or more nuclei are all foreign-body type. The findings are discussed in the light of current knowledge concerning giant cell formation. It is concluded that under the present experimental conditions, Langhans-type giant cells are the precursors of foreign-body-type giant cells.
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Pneumocystis pneumonia is a common component of the acquired immunodeficiency syndrome (AIDS) in the United States. Extrapulmonary pneumocystosis, however, is much less common. Rare cases have been reported in lymph nodes, bone marrow, spleen, pleura, gastrointestinal tract, liver, common bile duct, pancreas, skin, thyroid, and eye. A 39-yr-old man with history of chest wall injuries from gunshot and stabbing presented with multiple pleural masses clinically suspicious of metastatic deposits from an unknown primary. Fine-needle aspiration biopsy of the largest pleural mass revealed extrapulmonary pneumocystis, which led to the diagnosis of AIDS. Similar to the previous reports of pneumocystis mass lesions in extrapulmonary sites, the current case is associated with exuberant vascular proliferation and Langhans' giant cell reaction. Neovascularization and histiocytic influx from the newly formed blood vessels and Langhans' giant cell reaction seem to be a common tissue reaction to the massive deposition of pneumocystis organisms in extrapulmonary sites in patients with AIDS.
In the experimental tubulo-interstitial (anti-basement membrane) nephritis in the rat, electron microscopic studies after the in vivo microinjection of native ferritin in areas of granulomatous inflammation near the surface of the kidney indicate that epitheloid and multinucleate Langhans' giant cells are capable of endocytosis and particularly of micropinocytosis. This suggests the possibility that endocytotic activities as well as secretion phenomena are important in the immune defense mechanisms linked with these "specifically" developed cells.
The formation of multinuclear giant cells of the Langhans' type in tubulo-interstitial auto-immune nephritis in the rat has been investigated by means of autoradiography. While in the majority of giant cells all nuclei were radiolabeled, in a few both labeled and unlabeled nuclei were present. This latter finding represents strong evidence in favour of the hypothesis that giant cells do not form by endomitotic processes but rather through fusion of certain precursor cells. According to previous studies this precursor cell population consists mainly of epitheloid cells, i.e. modified monocytes.
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