Breaking T cell tolerance to beta cell antigens by merocytic dendritic cells

In type 1 diabetes (T1D), a break in central and peripheral tolerance results in antigen-specific T cells destroying insulin-producing, pancreatic beta cells. Herein, we discuss the critical sub-population of dendritic cells responsible for mediating both the cross-presentation of islet antigen to CD8⁺ T cells and the direct presentation of beta cell antigen to CD4⁺ T cells. These cells, termed merocytic dendritic cells (mcDC), are more numerous in non-obese diabetic (NOD), and antigen-loaded mcDC rescue CD8⁺ T cells from peripheral anergy and deletion, and stimulate islet-reactive CD4⁺ T cells. When purified from the pancreatic lymph nodes of overtly diabetic NOD mice, mcDC can break peripheral T cell tolerance to beta cell antigens in vivo and induce rapid onset T cell-mediated T1D in young NOD mouse. Thus, the mcDC subset appears to represent the long-sought critical antigen-presenting cell responsible for breaking peripheral tolerance to beta cell antigen in vivo.     

In situ demonstration of the activity of 3 beta-hydroxysteroid dehydrogenase on steroid hormone secreting cells within the paraaortic lymph nodes of golden hamster

The in situ activity of 3 beta-hydroxysteroid dehydrogenase was detected in clustered cells which showed steroid-producing morphology, within the capsule of the paraaortic lymph node. In light and electron microscopic studies, the positive reaction products were detected on intracapsular cell clusters. This result indicates that these unique cells may have a steroid secreting function within the lymph nodes.     

Lymph node metastases of EMT6 tumour in nude mice

Metastatic axillary lymph nodes following the injection of EMT6 tumour cells were observed in athymic nude mice, more often in female animals, and had a rapid growth rate. These metastases did not develop in syngeneic hosts. The latency of their appearance was inversely related to the number of injected cells.     

Lymph node metastases of EMT6 tumour in nude mice

Summary Metastatic axillary lymph nodes following the injection of EMT6 tumour cells were observed in athymic nude mice, more often in female animals, and had a rapid growth rate. These metastases did not develop in syngeneic hosts. The latency of their appearance was inversely related to the number of injected cells.We wish to thank Charles Gosse for breeding, maintenance and supply of the animals.     

Differences in utilization of tritiated thymidine and tritiated deoxycytidine by rat lymph node cells.

Large lymphoid cells and plasma cells in antigenically stimulated rat lymph nodes retain less label after injection of 3H-CdR than after injection of 3H-TdR. There is no difference amongst small lymphocytes. The data are consistent with a defect in the utilization of 3H-CdR in the late stages of B cell maturation in the rat.     

Cortisone sensitive T-cells in Peyers' patches.

Pretreatment of donor lymphoid cells with cortisone has been shown to depress the T-cell subpopulation responsible for cellular proliferation in the GVH reaction. A quantitative assay as well as the histological criteria of the GVH reaction have been used in this study to demonstrate the presence of cortisone-sensitive T-cells within the Peyer's patches as well as in the spleen and mesenteric lymph nodes in the rat.     

Degranulating activity in hybrid cells derived from rat peritoneal mast cells and ehrlich ascites tumor cells

Summary Fusion of rat mast cells and Ehrlich ascites tumor cells was mediated by HVJ. Compound 48/80-induced degranulation occurred in the fused cells formed from two mast cells and one tumor cell, but not in the fused cells from one mast cell and two or more tumor cells.I am grateful to DrK. Utsumi for valuable discussions and for the donation of HVJ.     

In situ demonstration of the activity of 3β-hydroxysteroid dehydrogenase on steroid hormone secreting cells within the paraaortic lymph nodes of golden hamster

Summary The in situ activity of 3-hydroxysteroid dehydrogenase was detected in clustered cells which showed steroid-producing morphology, within the capsule of the paraaortic lymph node. In light and electron microscopic studies, the positive reaction products were detected on intracapsular cell clusters. This result indicates that these unique cells may have a steroid secreting function within the lymph nodes.     

Differences in utilization of tritiated thymidine and tritiated deoxycytidine by rat lymph node cells

Summary Large lymphoid cells and plasma cells in antigenically stimulated rat lymph nodes retain less label after injection of³H-CdR than after injection of³H-TdR. There is no difference amongst small lymphocytes. The data are consistent with a defect in the utilization of³H-CdR in the late stages of B cell maturation in the rat.     

Fine structures of the basophil infiltration in regional lymph nodes of the guinea-pig after the intradermal injection of T cell mitogens

Basophil-rich infiltrates in regional lymph nodes of guinea-pigs were demonstrated by electron microscopy after the intradermal injection of T cell mitogens (PHA and Con A). Basophils infiltrated the stroma of the lymph node via the postcapillary venules (PCV) and migrated to the paracortex. Prior to infiltration of the lymph nodes a cutaneous basophil hypersensitivity reaction was seen in the mitogen-injected skin. B cell mitogen (LPS) injection did not induce this response.     

Fine structures of the basophil infiltration in regional lymph nodes of the guinea-pig after the intradermal injection of T cell mitogens

Summary Basophil-rich infiltrates in regional lymph nodes of guinea-pigs were demonstrated by electron microscopy after the intradermal injection of T cell mitogens (PHA and Con A). Basophils infiltrated the stroma of the lymph node via the postcapillary venules (PCV) and migrated to the paracortex. Prior to infiltration of the lymph nodes a cutaneous basophil hypersensitivity reaction was seen in the mitogen-injected skin. B cell mitogen (LPS) injection did not induce this response.     

Mechanisms of NK cell activation: CD4+ T cells enter the scene

Natural killer (NK) cells are innate lymphocytes involved in immunosurveillance through their cytotoxic activity and their capacity to secrete inflammatory cytokines. NK cell activation is necessary to initiate effector functions and results from a complex series of molecular and cellular events. We review here the signals that trigger NK cells and discuss recent findings showing that, besides antigen-presenting cells, T cells can play a central role in the initiation of NK cell activation in lymph nodes.     

Biological implications of preformed mast cell mediators

Mast cells store an impressive array of preformed compounds (mediators) in their secretory granules. When mast cells degranulate, these are released and have a profound impact on any condition in which mast cell degranulation occurs. The preformed mast cell mediators include well-known substances such as histamine, proteoglycans, proteases, and preformed cytokines, as well as several recently identified compounds. Mast cells have recently been implicated in a large number of novel pathological settings in addition to their well-established contribution to allergic reactions, and there is consequently a large current interest in the molecular mechanisms by which mast cells act in the context of a given condition. In many cases, preformed mast cell mediators have been shown to account for functions ascribed to mast cells, and these compounds are hence emerging as major players in numerous pathologies. In this review we summarize the current knowledge of preformed mast cell mediators.     

Mast cells are present during angiogenesis in the chick extraembryonic vascular system

The extraembryonic vascular membranes of 3-day-18-day chick embryos were examined for the presence of mast cells. As early as 3.5 days mast cells were found on the area vasculosa. It is suggested that these cells have a role in angiogenesis of the chick extraembryonic vascular system.     

Mast cells are present during angiogenesis in the chick extraembryonic vascular system

Summary The extraembryonic vascular membranes of 3-day-18-day chick embryos were examined for the presence of mast cells. As early as 3.5 ddays mast cells were found on the area vasculosa. It is suggested that these cells have a role in angiogenesis of the chick extraembryonic vascular system.The work is supported by The Wellcome Trust.     

A combined histochemical and autoradiographic study of the distribution and maturation of peritoneal mast cells in the rat

Summary The relationship of mitotic activity and degree of cytological differentiation for mast cells of the peritoneal cavity of the rat was studied using combined autoradiographic and histochemical techniques. A mitotic pool of mast cells can be differentiated from a non-mitotic pool, the former containing cells with immature cytoplasmic differentiation and the latter with fully developed cytoplasmic histochemical properties.     

Differenzierungsmethode metachromatischer Zellen nach ihrem Säuregrad

Summary A method is described for histochemical definition of the metachromatic substance of mast cells. A slide of tissue containing mast cells is treated with substances dissolving metachromasia, such as hyaluronidase and water, and later on stained in aqueous solutions of gradually heightened pH. A marked spot of the slide is counted at each pH. Concentrations of hydrogen and numbers of mast cells result in a characteristic curve.     

Immunocytochemical demonstration of calmodulin in cells secreting by exocytosis

Calmodulin is a regulator of several calcium-dependent cellular processes. It has been suggested that it plays a role in the mechanism of secretion. Employing an indirect immunoperoxidase technique at the light microscope level, this study demonstrates the presence of calmodulin in several exocytotic cells (mast cells, thyroid follicular cells, neurohypophyseal neurosecretory terminals, pancreatic beta-cells and pancreatic acinus cells) in rat and man. The positive staining reaction for calmodulin was granular and at least in the case of rat mast cells it appeared to be associated with the granule membrane.     

Cortisone sensitive T-cells in Peyer's patches

Summary Pretreatment of donor lymphoid cells with cortisone has been shown to depress the T-cell subpopulation responsible for cellular proliferation in the GVH reaction. A quantitative assay as well as the histological criteria of the GVH reaction have been used in this study to demonstrate the presence of cortisone-sensitive T-cells within the Peyer's patches as well as in the spleen and mesenteric lymph nodes in the rat.This work was supported by a grant of the Délégation Générale à la Recherche Scientifique et Technique (No. 74-7-0619).