Intravascular Lymphocytes Research Articles

Intrapulmonary T Cells Are Sufficient for Schistosoma-Induced Pulmonary Hypertension.

Schistosomiasis is a parasitic infection that can cause pulmonary hypertension (PH). Th2 CD4 T cells are necessary for experimental Schistosoma-PH. However, if T cells migrate to the lung to initiate, the localized inflammation that drives vascular remodeling and PH is unknown. Mice were sensitized to Schistosoma mansoni eggs intraperitoneally and then challenged using tail vein injection. FTY720 was administered, which blocks lymphocyte egress from lymph nodes. T cells were quantified using flow cytometry, PH severity via heart catheterization, and cytokine concentration through ELISA. FTY720 decreased T cells in the peripheral blood, and increased T cells in the mediastinal lymph nodes. However, FTY720 treatment resulted in no change in PH or type 2 inflammation severity in mice sensitized and challenged with S. mansoni eggs, and the number of memory and effector CD4 T cells in the lung parenchyma was also unchanged. Notably, intraperitoneal Schistosoma egg sensitization alone resulted in a significant increase in intravascular lymphocytes and T cells, including memory T cells, although there was no significant change in parenchymal cell density, IL-4 or IL-13 expression, or PH. Blocking T cell migration did not suppress PH following Schistosoma egg challenge. Memory CD4 T cells, located in the lung intravascular space following egg sensitization, appear sufficient to cause type 2 inflammation and PH.

Cutaneous intravascular NK/T cell lymphoma: a case report

An 18-year-old female presented with painful erythema and nodules on both legs for more than 2 years.Dermatological examination showed irregularly sized,mildly indurated,tender,deep subcutaneous nodules arising in diffused infiltrated dark erythematous patches in the inner and posterior region of the left leg.Histopathology showed no significant changes in the epidermis.There were perivascular lymphoid cell infiltrates in the dermis and subcutis.Multiple sites of necrosis of blood vessel walls with vascular occlusions were noted.The lumens of some blood vessels were filled with lymphocytes,among which were many atypical cells with hyperchromatic nuclei and pathologic mitotic figures.Immunohistochemistry showed that lymphocytes in the cavities of blood vessels were positive for CD3(+++),CD3e(+++),CD2(+),CD56(+++),granzyme B(+++),perforin(+++),CD30(+),Ki67 (+++,100％ ),but negative for CD20,CD5,CD7,CD4,CD8,TdT,anaplastic lymphoma kinase,early membrane antigen (EMA) or pan cytokeratin (pCK).The endothelial cells lining the blood vessels stained positively for CD34.The intravascular lymphocytes were also positive for EBER1/2 by in situ hybridization.A diagnosis of cutaneous intravascular NK/T cell lymphoma was made. Key words: Lymphoma,non-Hodgkin; Case reports [Publication type]

Cracking Spaces in Hashimoto Thyroiditis Are Lymphatic and Prelymphatic Vessels

A century ago Hashimoto described the histologic hallmarks of struma lymphomatosa: (1) lymphoid follicles, (2) changes in the epithelial cells, (3) formation of connective tissue, and (4) diffuse round cell infiltration. He also showed some cracking spaces close to lymphoid follicles resembling vessels. The aim of this study was to investigate the possible lymphatic nature of these spaces and their prevalence in non-neoplastic thyroid tissue. Ten cases of Hashimoto thyroiditis (HT), 5 of Basedow-Graves disease (BG), and 5 of normal thyroid tissue (NT) were selected. Tissues were stained with hematoxylin and eosin, CD31 (Dako), and D2-40 (Dako) stains. Cracking spaces staining positive for CD31 and D2-40 stains were considered as lymphatic vessels. Site, distribution, intravascular valves and lymphocytes, perivascular lymphoid aggregates, and number and surface of lymphatic vessels were evaluated using a computer-assisted digital videocamera microscope (Nikon digital sigh, DS-2Mv). The number of lymphatic vessels increased from NT [3 (range, 2 to 13)] to BG [8 (range, 5 to 9)] to HT [12.5 (range, 10 to 16)]. A significant statistical difference was observed within the group (P=0.003): HT differed from NT (P=0.016) and BG (P=0.002). The area of lymphatic vessels increased from NT [0.01 mm (range, 0.01 to 0.12 mm2)] to BG [0.03 mm2 (range, 0.01 to 0.19 mm2)] to HT [0.03 mm (range, 0.01 to 0.6 mm2)]. A significant statistical difference was observed among the groups (P=0.001): NT differed from HT (P<0.001) and from BG (P<0.001). Lymphatic vessels showed valves, perivascular lymphoid aggregates, and intravascular lymphocytes. The cracking spaces shown by Hashimoto are mainly lymphatic vessels and represent a characteristic feature of autoimmune thyroid diseases.

Intravascular large cell lymphoma

A 19‐year‐old female presented at our hospital with a 1‐year history of a 5‐cm indurated nontender lesion on the left shoulder. Two months later, a similar lesion appeared in the left mammary region, accompanied by necrosis and fever.At admission to our department, she presented disseminated lesions in the left submandibular region, the sternal area and the posterior part of the upper and lower extremities.The lesions were indurated erythematous‐violaceous plaques affecting the adipose tissue, some with ulcerations and necrotic crusting (Fig. 1). The first histopathological report was thrombosis of the capillary vessels and focal vasculitis (Fig. 2).Ulceration and necrotic crusting lesion in the left mammary regionimageHistopathology showing dilation of thrombosed vessels with fibrin deposits (hematoxylin and eosin, magnification ×244)imageA biopsy from a lesion on the left thigh showed dilated vessels with large atypical intravascular cells with hyperchromatic nuclei and numerous atypical mytoses in the dermis and subcutaneous tissue. Some of these cells were immersed in fibrin thrombi or in the perivascular connective tissue (Fig. 3). An immunohistochemical study was positive for the common leukocytic antigen and for the B‐cell phenotype. The diagnosis was large B‐cell lymphoma. The patient persisted with a high fever, dry cough, pericardial effusion complicated by an abscess and left pleural effusion. She died before systemic workings for lymphoma could be carried out, and before chemotherapy could be attempted.Histopathology showing atypical intravascular lymphocytes (hematoxylin and eosin, magnification ×366)image

Ultrastructural identification and distribution of the adhesion molecules ICAM-1 and LFA-1 in the vascular and extravascular compartments of the human palatine tonsil.

Immunohistological analysis of sections prepared from human palatine tonsils revealed marked differences in the distribution of the adhesion molecule, leucocyte function antigen-1 (LFA-1) and its counter receptor, intercellular adhesion molecule-1 (ICAM-1). Light microscopy showed that LFA-1 was restricted to the leucocytes, particularly the lymphocytes. In contrast, staining of ICAM-1 was predominantly confined to the vascular endothelium with the greatest expression seen on the morphologically distinct high endothelial venules in the parafollicular areas; these are the sites that appear to support lymphocyte migration. Electron microscopy revealed that ICAM-1 was present on the luminal and lateral surfaces of the high endothelium and absent from the abluminal surface supported by basal lamina. The ICAM-1 was also absent from those surfaces of the endothelium that were in close contact with intravascular lymphocytes. Other cells stained by the anti-ICM-1 antibody included dendritic cells, plasma cells and epithelial cells in the reticulated crypt epithelium and in the upper strata of the non-keratinised stratified squamous epithelium. The high expression of LFA-1 was most prominent on lymphocytes, low on antigen-presenting cells and activated lymphoid cells, and not detectable on plasma cells, epithelial and endothelial cells. We propose that LFA-1/ICAM-1 binding participates in mediating the transendothelial migration of lymphocytes across the high endothelial venules of palatine tonsil.

Tannic-acid staining material on high endothelial venules and lymphocytes in skin and peripheral lymph nodes in Staphylococcus aureus-associated erythroderma

The recognition and binding of glycoprotein receptors on lymphocytes to specific antigens present on high endothelial venules (HEV) precedes the egress of lymphocytes from the blood stream into the tissues. In this paper, we report the presence of HEVs with tannic-acid staining material (TASM+ HEVs) in Staphylococcus aureus-associated erythroderma, which allow the migration of CD8+ lymphocytes from the bloodstream into the epidermis. TASM positivity is also expressed on lymphocytes within the regional lymph nodes, and by intravascular lymphocytes prior to leaving the TASM+ HEV. It is proposed that TASM positivity may represent a molecule, which may function in binding lymphocytes to HEVs prior to egress from the HEV. (TASM is lost from lymphocytes after leaving the HEVs). The expression of TASM positivity may form an essential part of the CD8+ lymphocyte-HEV recognition system, and may be the means whereby CD8+ lymphocytes generated in the regional lymph nodes by various mitogens (in this case by staphylococcal mitogens) may 'home' to specific sites within the epidermis. TASM positivity on both the HEVs and lymphocytes may serve as a convenient marker of such a system.

The physiological role of the lung in lymphocyte migration.

The high numbers of lymphocytes found in the lungs early after i.v. injection of labelled cells have often been interpreted as a passive filter function of the first capillary bed lymphocytes have to pass. When normal human lung tissue had been digested, large numbers of lymphocytes were recovered, which approximately amount to the same pool size as the peripheral blood pool (1). Intravascular lymphocytes have been demonstrated histologically in perfusion-fixed lungs (2). One aim of the present study was therefore to find out whether the early homing, at 30 min, of up to 40% of the i.v. injected lymphocytes (3,4,5) is a physiological phenomenon or an artifact. The homing to the lung after i.v. and after intraaortal injection of labelled lymphocytes was compared. The pool size of the pulmonary vascular system was quantitated by extracorporeal perfusion and collection of lymphocytes in the venous effluent. Similar perfusions were carried out with segments of the liver and kidney for comparison. Finally, lymphocytes homing to the lung and being released from it were characterized by surface markers. Normal young pigs were used because the migration kinetics of lymphocytes to lymphoid and non-lymphoid organs are well described in this species (5,6), and the lungs are large enough for a controlled ex vivo perfusion with a system previously used for spleen perfusion (7).KeywordsEuropean Economic CommunityCircuit PerfusionEarly HomingBlood LungMigration KineticThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Endovascular papillary angioendothelioma of childhood: A vascular lesion possibly characterized by “High” endothelial cell differentiation

Two cases of endovascular papillary angioendothelioma (EPA) of the skin were studied immunohistochemically to assess the expression of endothelial, leukocytic, and epithelial determinants by these lesions. The tumor cells in both cases were labeled by antibodies to Factor VIII-related antigen, vimentin, and blood group isoantigens; they also bound Ulex europaeus I agglutinin. On the other hand, immunoreactivity for epithelial membrane antigen, Leu-M1, HLA-DR (Ia-like antigen), and leukocyte common antigen (LCA) was not observed. Stromal and intravascular lymphocytes were labeled intensely with antibodies to LCA and HLA-DR and were intimately associated with papillary configurations of proliferating intravascular tumor cells. These results confirm the endothelial nature of EPA and suggest that the cells of this lesion may differentiate toward "high" endothelial cells, which have been shown to interact functionally with circulating lymphocytes.

Endovascular papillary angioendothelioma of childhoodaA vascular lesion possibly characterized by “High” endothelial cell differentiation

Two cases of endovascular papillary angioendothelioma (EPA) of the skin were studied immunohistochemically to assess the expression of endothelial, leukocytic, and epithelial determinants by these lesions. The tumor cells in both cases were labeled by antibodies to Factor VIII-related antigen, vimentin, and blood group isoantigens; they also bound Ulex europaeus I agglutinin. On the other hand, immunoreactivity for epithelial membrane antigen, Leu-M1, HLA-DR (Ia-like antigen), and leukocyte common antigen (LCA) was not observed. Stromal and intravascular lymphocytes were labeled intensely with antibodies to LCA and HLA-DR and were intimately associated with papillary configurations of proliferating intravascular tumor cells. These results confirm the endothelial nature of EPA and suggest that the cells of this lesion may differentiate toward “high” endothelial cells, which have been shown to interact functionally with circulating lymphocytes.

The permeability of the blood-brain barrier in mice suffering from fatal lymphocytic choriomeningitis virus infection.

The ultrastructure and the blood-brain-barrier (BBB) permeability were studied in mice suffering from lymphocytic choriomeningitis (LCM). Brains and meninges from mice suffering from LCM virus-induced lymphocytic choriomeningitis were studied by investigating the BBB function and by electron and light microscopy. The cellular exudate in the leptomeninges was located in the subarachnoid space, in arachnoidea and pia, and it was dominated by proliferated pial cells and mononuclear cells, most of which were lymphocytes, while there were only a few neutrophil granulocytes. Many intravascular lymphocytes were seen adhering to as well as penetrating the vessel walls. Many of these lymphocytes were morphologically compatible with T cells. Lymphocytes and larger mononuclear cells were also accumulated in the choroid plexus, and lymphocytes were present in the ventricular system with a tendency to adhere to ependymal epithelial cells. Inspection of the ultrathin sections incubated for horseradish peroxidase (HRP)-activity revealed that the overwhelming part of the peroxidase activity was localized in the extracellular space of the meningeal vessel walls and especially in the abundant intercellular fluid which, like the inflammatory cells, was found in the subarachnoid space in arachnoidea and in pia. In the neuropil, only very small quantities of reaction product were seen intercellularly in the most superficial layers of the cortex. The tight junctions were always intact, but the possibility of a non-demonstrable opening is discussed. Evaluation of the BBB permeability for 2-amino[1-14C]isobutyric acid (AIB) was made by quantitative autoradiography, and it was demonstrated convincingly that AIB concentrations in the subpial and perichorodial tissues were markedly increased in diseased animals as compared to the controls. Our results seem to contradict previous theories on the cause of death resulting from the LCM disease. The findings presented here do not speak in favor of a pronounced brain edema, just as results obtained by us and others do not speak for the possibility of the death being caused by convulsive seizures with subsequent brain anoxia. However, our observations are compatible with the hypothesis that cytotoxic T cells may interact in vivo with virus-infected targets, which are essential for the regulation of the composition of the cerebrospinal fluid. On the other hand, the dysfunction of the BBB demonstrated adds a new element to the pathologic mechanism in a model for the study of virus-induced meningitis.

Heat Production by Lymphocytes in Chronic Lymphocytic Leukaemia

Using microcalorimeters of the thermopile conduction type heat production was measured in lymphocytes from peripheral blood in 8 normals and 10 patients with chronic lymphocytic leukaemia (CLL). The heat production per CLL lymphocyte was lower (1.8 pW/cell) than that found in normal lymphocytes (2.6 pW/cell). Due to the high numbers of lymphocytes in the peripheral blood the estimated heat production of the intravascular lymphocyte pool in CLL was considerably higher than in normals. Since the circulating lymphocytes constitute a minute fraction of the total lymphoid mass in CLL it is suggested that the accumulation of metabolically active lymphocytes in blood and tissues may explain the common clinical signs of hypermetabolism in this disease. The results also indicate that calorimetry may be a useful technique for metabolic studies in suspensions of malignant cells.

The effect of Hydrocortisone on the kinetics of normal human lymphocytes

Lymphocyte kinetic studies employing 51-chromium-labeled autologous lymphocytes were performed in nine normal volunteers in order to determine the effects of hydrocortisone administration on the recirculating versus the nonrecirculating intravascular lymphocyte pools. Following infusion of labeled cells, the recirculating portion of the labeled cells rapidly equilibrated with the total intravascular lymphocyte pool and the vastly larger total-body recirculating lymphocyte pool, so that by 1 hr following infusion 21.8% plus or minus 3.2% of the labeled lymphocytes were left in the circulation. Four hundred milligrams of intravenous hydrocortisone administered 24 hr after infusion of labeled cells caused a profound but transient lymphocytopenia which was maximal at 4 hr with return of lymphocyte counts to normal by 24 hr after injection. Concomitant with the lymphocytopenia there was a dramatic increase in lymphocyte specific activity (cpm per 10–6 lymphocytes), while the total lymphocyte- associated radioactivity remaining in the circulation was unchanged, indicating that corticosteroid administration depleted the unlabeled recirculating cells. As the lymphocyte counts returned to normal following hydrocortisone, the specific activity also returned to normal. These studies indicated that hydrocortisone administration caused a transient lymphocytopenia by a preferential depletion of the recirculating portion of the intravascular lymphocyte pool.

The Effect of Hydrocortisone on the Kinetics of Normal Human Lymphocytes

Lymphocyte kinetic studies employing 51-chromium-labeled autologous lymphocytes were performed in nine normal volunteers in order to determine the effects of hydrocortisone administration on the recirculating versus the nonrecirculating intravascular lymphocyte pools. Following infusion of labeled cells, the recirculating portion of the labeled cells rapidly equilibrated with the total intravascular lymphocyte pool and the vastly larger total-body recirculating lymphocyte pool, so that by 1 hr following infusion 21.8% plus or minus 3.2% of the labeled lymphocytes were left in the circulation. Four hundred milligrams of intravenous hydrocortisone administered 24 hr after infusion of labeled cells caused a profound but transient lymphocytopenia which was maximal at 4 hr with return of lymphocyte counts to normal by 24 hr after injection. Concomitant with the lymphocytopenia there was a dramatic increase in lymphocyte specific activity (cpm per 10-6 lymphocytes), while the total lymphocyte-associated radioactivity remaining in the circulation was unchanged, indicating that corticosteroid administration depleted the unlabeled recirculating cells. As the lymphocyte counts returned to normal following hydrocortisone, the specific activity also returned to normal. These studies indicated that hydrocortisone administration caused a transient lymphocytopenia by a preferential depletion of the recirculating portion of the intravascular lymphocyte pool