The lymphadenopathy of HIV infection.
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AIDS-Related Complex↗
Biomedical subjects
S Uccini
Publications and source records attributed to S Uccini.
Expression of adhesion molecules in Langerhans' cell histiocytosis.
Expression of adhesion molecules was investigated in six biopsy specimens of Langerhans' cell histiocytosis using immunocytochemistry. Cells with Langerhans' cell histiocytosis morphology were stained for ICAM-1, for the beta-1 integrins alpha-4 (VLA-4) and alpha-5 (VLA-5) , and for the beta-2 integrins LFA-1, MAC-1 and p150,95. This pattern of reactivity was different from that of epidermal Langerhans' cells of the normal skin which were not immunostained. A variable number of CD68+ multinucleated giant cells was present in five biopsies. They were less reactive than the cells of Langerhans' cell histiocytosis for alpha-4 (VLA-4) and LFA-1, were positive for MAC-1 and p150,95 and were characterized by prominent expression of the beta-1 integrins alpha-2 (VLA-2), alpha-3 (VLA-3) and of VnR (alpha-v/beta-3). The repertoire of adhesion molecules expressed by giant cells is indicative of profound cell-matrix interactions, whereas that of Langerhans' histiocytosis cells suggests particularly active cell-cell interactions. Blood vessels of the lesions were stained for beta-1 integrins, for vitronectin receptor and for molecules involved in adhesion and trans-endothelial migration of circulating leukocytes, such as ICAM-1, VCAM-1 and E-selectin. Additional findings were the observation of CD1a + multinucleated giant cells in a single case, suggesting a possible lineage relationship with the histiocytosis cells, and the demonstration of some Ki-67+ Langerhans' cell histiocytosis cells and CD1a+ mitotic figures in four of six cases, indicating local proliferation of Langerhans' histiocytosis cells.
Adult↗
Detection of HIV-1 genome in lymph-node biopsies by polymerase chain reaction: a useful tool for epidemiological studies.
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Biopsy↗
Synaptophysin in human breast carcinomas.
Synaptophysin expression was studied immunohistochemically in 109 female and in three male breast carcinomas. Positivity was demonstrated in 10 female and in two male tumours in a high percentage of neoplastic cells. Synaptophysin positive breast carcinomas also expressed other neuroendocrine markers such as chromogranin and neuron-specific enolase.
Adult↗
High frequency of Epstein-Barr virus genome detection in Hodgkin's disease of HIV-positive patients.
Lymph nodes obtained from 7 HIV-positive and 20 HIV-negative patients with Hodgkin's disease were examined for the presence of Epstein-Barr virus antigens and genome. EBV antigens were observed in only 2 out of 20 HIV-negative patients, whereas lymph nodes of HIV-positive patients did not reveal evidence of EBV antigens. By in situ hybridization and Southern blot analysis, EBV genome was found in 5 out of 7 HIV-positive patients; the EBV genome was detected in the nucleus of Reed-Sternberg and Hodgkin's cells. EBV DNA was observed by in situ hybridization and Southern blot analysis in only 3 out of 20 HIV-negative patients with Hodgkin's disease. In both groups, Reed-Sternberg and Hodgkin's cells were negative for C3d EBV receptor. Our results show a statistically significant increased expression of EBV DNA in HIV-positive patients with Hodgkin's disease, as compared with HIV-negative patients with HD.
Adolescent↗
Macrophages and interdigitating reticulum cells in normal human thymus and thymomas: immunoreactivity for interleukin-1 alpha, interleukin-1 beta and tumour necrosis factor alpha.
Pairs of monoclonal/polyclonal antibodies directed against interleukin-1 (IL-1) alpha, IL-1 beta and tumour necrosis factor (TNF) alpha were used for immunocytochemical identification of cytokine-containing cells in cryostat sections of human fetal thymuses and thymomas. In the fetal thymus immunoreactivity for IL-1 alpha was mainly confined to the medulla and was detected in S-100 positive interdigitating reticulum cells. The pattern of immunoreactivity for IL-1 beta was similar to that for IL-1 alpha, but the number of positive cells was much lower. Cells positive for TNF alpha were extremely rare in the fetal thymus. In 11 thymomas macrophages were constantly present and were regularly distributed throughout the tumour, whereas S-100 positive interdigitating reticulum cells were fewer and were characterized by a zonal distribution. Thymoma-associated macrophages were negative for IL-1 beta and were poorly reactive for IL-1 alpha, only a few positive cells being detected in five of the cases. Some macrophages with immunoreactivity for TNF alpha were detected in seven cases; they formed rosettes with surrounding lymphocytes or were located in a perivascular position. A marked immunoreactivity for TNF alpha was constantly detected in mast cell granules, which were observed in nine thymomas but not in fetal thymus. Positive immunoreactivity of interdigitating reticulum cells for IL-1 alpha was confirmed in five reactive lymph nodes and was also observed in Langerhans' cells in dermatopathic lymphadenitis. Our findings suggest that IL-1 alpha is a crucial molecule for interdigitating reticulum cell and Langerhans' cell function.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Cytokine production (IL-1 alpha, IL-1 beta, and TNF alpha) and endothelial cell activation (ELAM-1 and HLA-DR) in reactive lymphadenitis, Hodgkin's disease, and in non-Hodgkin's lymphomas. An immunocytochemical study.
Cryostat sections of 58 lymph nodes were immunostained with a polyclonal rabbit serum against IL-1 alpha, and with monoclonal antibodies directed to IL-1 alpha (Vmp18), IL-1 beta (Vhp20 and BRhC3), and tumor necrosis factor alpha (TNF alpha) (B154.7). Furthermore the presence of cytokine-containing cells was correlated with the expression of endothelial leukocyte adhesion molecule (ELAM-1; 29F2) and of human leukocyte antigen (HLA-DR) (OKIa-1) by endothelial cells. Cells containing IL-1 and/or TNF alpha were detected mainly in pathologic conditions characterized by reactive or neoplastic expansion of the lymph node paracortex. Cells positive for IL-1 were detected in 16 of 21 cases of Hodgkin's disease, in 4 of 4 cases of T-NHL, and in 5 cases of diffuse or mixed lymphadenitis. Interleukin-1 alpha was detected in macrophages, interdigitating reticulum cells (IDRCs), endothelial cells, and neoplastic Hodgkin's and Reed-Sternberg (H-RS) cells. Cells positive for IL-1 beta were much fewer and consisted mainly of macrophages. Hodgkin's Reed-Sternberg cells were negative for IL-1 beta even after in vitro stimulation with bacterial endotoxin. Tumor necrosis factor alpha (TNF alpha) was present in macrophages and H-RS cells. Endothelial leukocyte adhesion molecule-1 expression by endothelial venules was detected in 17 of 20 cases of Hodgkin's disease, in 2 of 4 cases of T-NHL, and in 5 of 5 cases of diffuse lymphadenitis. In these pathologic conditions, HLA-DR antigens also were expressed frequently by endothelial cells. Cytokine-containing cells and ELAM-1-positive high endothelial venules (HEV) were extremely rare in lymph nodes involved by follicular lymphadenitis (12 cases) or B-NHL (16 cases). In cases of reactive or neoplastic B-cell proliferations, HLA-DR-positive HEVs still were present often. Our results indicate that IL-1/TNF alpha production at tissue level is often associated with ELAM-1 expression by HEVs, but is less well correlated with expression of HLA-DR antigens by endothelial cells.
Adolescent↗
Lymph nodes in HIV-positive drug abusers with persistent generalized lymphadenopathy: histology, immunohistochemistry, and pathogenetic correlations.
Persistent generalized lymphadenopathy (PGL) represents an important aspect of the natural history of AIDS. It is a reactive lymphadenitis appearing in HIV-positive drug abusers and homosexual men, involving lymph nodes mostly located in the neck and in axillary regions. This present review chapter describes the most salient histological and immunohistochemical features of lymph nodes of intravenous drug abusers affected by PGL. Microscopic changes are homogeneous and essentially comparable allowing to subgroup nodes according to their histologic pattern: those with hyperplastic and those with regressive changes. Hyperplastic changes include hyperplasia of germinal centers without or with fragmentation and vascularization, and increased postcapillary venules in the paracortex. Regressive changes are characterized by follicular involution and by follicular depletion with or without fibrosis. Immunohistologic phenotyping shows a peculiar infiltration of CD3/CD8+ lymphocytes in germinal centers and a progressive lysis of follicular dendritic reticulum cells. The presence of HIV antigens can be demonstrated in germinal centers with a reticular pattern paralleling that of follicular dendritic reticulum cells, in endothelial cells of paracortical venules, and in sinus macrophages. Furthermore, HIV genome is sometimes detectable by in situ hybridization in a few endothelial and mononuclear cells of the paracortex. Epstein Barr virus (EBV) antigens are occasionally observed in a few lymph node cells, while EBV genome seems to be absent during the PGL phase of the HIV infection. In conclusion, during PGL, immunohistologic features correlate well with the extent of the histologic changes.
AIDS-Related Complex↗
High frequency of Epstein-Barr virus genome in HIV-positive patients with Hodgkin's disease.
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Adolescent↗
Expression of macrophage-associated antigens in tissues involved by Langerhans' cell histiocytosis (histiocytosis X).
The expression of macrophage antigens KP1, Mac, lysozyme, and alpha-1-antichymotrypsin was investigated on routine paraffin sections from 17 cases of Langerhans' cell histiocytosis (LCH). All the major clinical forms were represented, including single lesions and monosystemic and multisystemic disease. In all the cases, a variable fraction (3-35%) of LCH cells was immunoreactive with KP1 and anti-Mac; the staining pattern was quite typical because the immunoreaction product was often confined to the perinuclear space and the Golgi area. LCH cells containing lysozyme and AACT were detected less frequently; however, in positive cases the percentage of LCH cells immunoreactive for lysozyme and AACT was in the same range as that of KP1-positive cells. On immunostained cytosmears (one case), about 10% of the CD1a-positive cell population was reactive for the macrophage antigens CD14 and PAM-1. No association was noted between the number of KP1-positive cells and the clinical form and/or anatomic site of the lesion. Phagocytic macrophages were significantly and diffusely immunoreactive with KP1 and anti-Mac and for AACT and lysozyme. Multinucleated giant cells with irregular nuclei were frequently observed; these cells were rarely S-100 positive, were consistently stained by KP1 and AACT, and were occasionally anti-Mac positive. The authors' findings suggest that antimacrophage monoclonals, in conjunction with S-100 protein, may represent a useful tool to establish the diagnosis of LCH in paraffin-embedded material.
Antibodies, Monoclonal↗
Human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) antigens and genome in lymph nodes of HIV-positive patients affected by persistent generalized lymphadenopathy (PGL).
The presence of human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) antigens and genome has been investigated in 50 lymph nodes involved by persistent generalized lymphadenopathy (PGL). All the patients were HIV infected and most of them (42 of 50) also had anti-EBV serum antibodies. At lymph node level, HIV and EBV antigens were studied by immunohistochemistry using monoclonal antibodies directed against viral core proteins. The HIV p24 protein was detected in 43 of 50 lymph nodes within the B-cell germinal centers with a reticular pattern. Few cells with positive results for EBV antigens were found in only 2 of 50 lymph nodes. These rare EBV-positive centrocyte-like cells were mainly located in the germinal centers. The presence of HIV and EBV genome was also studied in lymph nodes involved by PGL, with the use of in situ and Southern blot hybridization. A positive reaction for HIV genome was detected in only 1 of 14 lymph nodes with the Southern blot hybridization, and the presence of EBV genome was never demonstrated in these lymph nodes with the use of both in situ and Southern blot hybridization. The expression of EBV antigens and genome was also investigated in the peripheral blood of 15 patients with PGL in which cells with positive results for EBV antigens were detected in a single case with a frequency of 1 X 10(-4). No evidence of EBV genome was found with the use of the in situ hybridization. These results suggest that EBV is not present in lymph nodes during the PGL phase and that its possible implication in the pathogenesis of acquired immune deficiency syndrome (AIDS)-associated lymphoma might be a late event.
Adolescent↗
The Langerhans' cells.
The morphological, enzymatical, immunocytochemical and functional properties of Langerhans' cells are briefly reviewed. Langerhans' cells are located mainly in the squamous stratified epithelia, but are also present in the thymus and in superficial lymphnodes. At the ultrastructural level, they are characterized by unique cytoplasmic organelles, the Birbeck granules, whose function is still unknown. Langerhans' cells possess strong ATPase activity and are weakly positive for alpha-naphtyl acetate esterase and for acid phosphatase; they are immunoreactive for CD1a (T6), class II MHC antigens and S-100 protein. In some pathological conditions, like dermatopathic lymphadenopathy and Langerhans' cell histocytosis, Langerhans' cells also are characterized by the expression of monocyte-macrophage antigens. Langerhans' cells act as antigen-presenting cells to T lymphocytes; their functional capacity is strictly dependent on the levels of expression of class II MHC antigens. Langerhans' cells are of bone marrow origin and are derived from a circulating precursor which is probably related to the monocyte.
Animals↗
Interaction of HIV and EBV at lymphoid tissue level: immunohistochemistry and in situ hybridization.
The presence of Epstein-Barr virus antigens and genome was studied in lymph nodes from HIV + patients affected by PGL. Cryostat sections from 50 lymph nodes of HIV + patients were immunostained with EBV-VCA (viral capsid antigen), EBV-EA (early antigen) and p24 HIV major core protein monoclonal antibodies. In situ hybridization was performed using a biotin conjugated EBV DNA probe; the reaction product was demonstrated by immunohistochemical method. As positive controls, EBV producer B95-8 and HIV infected H9 cell lines were used. The majority of patients had circulating EBV antibodies mainly directed against the viral capsid antigen and only in few cases against early antigens. Positivity for HIV p24 protein was detected in 43 out of 50 lymph nodes within the germinal centers with a reticular pattern. Only 2 out of 50 lymph nodes presented very few positive cells for EBV antigens and none expressed detectable EBV genome. Our results suggest that EBV cellular expression does not correlate with serum positivity; furthermore the absence of EBV antigens and genome at tissue level might indicate that EBV is not directly involved in the pathogenesis of PGL.
AIDS-Related Complex↗
Immunoreactivity for IL-1 beta and TNF alpha in human lymphoid and nonlymphoid tissues.
Monoclonal antibodies (MAbs) against two non-cross-reacting antigens of human IL-1 beta (Vhp20 and BRhC3) and human TNF alpha (B154.2 and B154.7) were applied to identify cytokine-containing cells in tissue sections and in cell suspensions. IL-1 beta- or TNF alpha-positive cells were not present in immunostained cytocentrifuge smears prepared from freshly isolated peripheral blood leukocytes, spleen, and lymph node cells. After 18 hours of culture with bacterial endotoxin (LPS), 80% to 90% of blood monocytes, 30% of spleen macrophages, and 2% to 28% of lymph node macrophages were strongly positive for IL-1 beta with either of the MAbs. Furthermore, 25% to 35% of blood monocytes and 6% to 60% of lymph node macrophages were stained for TNF alpha. Cells positive for IL-1 beta or TNF alpha were extremely rare in sections of normal thymus, spleen, and lymph nodes. Immunoreactivity for IL-1 beta or TNF alpha was frequently observed in sections of granulomatous lymphadenitis (N = 11). IL-1 beta or TNF alpha staining was confined to the epithelioid macrophages forming the granuloma, and the intensity of TNF alpha reactivity was generally stronger. The high frequency of cytokine-containing cells in this pathologic condition was confirmed in a cell suspension study showing that 20% of epithelioid macrophages were weakly positive for IL-1 beta and 80% were strongly positive for TNF alpha. The presence of cytokine-containing cells was investigated in cryostat sections of several nonlymphoid organs with normal histologic appearance. IL-1 beta reactivity was not observed in any of the tissues. TNF alpha reactivity was frequently demonstrated in isolated macrophages embedded in the interstitial connective tissue.
Humans↗
Letterer-Siwe disease: immunohistochemical evidence for a proliferative disorder involving immature cells of Langerhans lineage.
The morphological, ultrastructural and immunophenotypic properties of Histiocytosis-X (H-X) cells were investigated in a lymph node involved by Letterer-Siwe (L-S) disease. H-X cells were T6+ (CD1a), S-100+, T4+ (CD4) and HLA-DR+; in addition they were consistently T11+ (CD2) and were stained by antibodies directed against receptors for transferrin (T9), C3bi (OKM-1/CD11b), IgG-Fc (Leu-11/CD16) and Interleukin-2 (IL-2R/CD25). On immunostained cytosmears, T6+ cells were highly polymorphic and a prominent fraction (45%) showed immature morphology, characterized by lymphoid appearance. Cells expressing macrophage markers (ANAE, AACT, Leu-M3/CD14, PAM-1) were 10-fold fewer than T6+ cells and did not show a lymphoid morphology. At TEM level, H-X cells were characterized by poor content of LC granules and by the presence of myelin-like laminated bodies and of lysosome-like dense bodies. The immunophenotypic properties of H-X cells were compared to those of epidermal Langerhans cells (LCs) and of LCs present in lymph nodes of three cases of dermatophatic lymphadenitis. Epidermal LCs were T6+/HLA-DR+, and sometimes faintly T4+. Lymph node LCs were T6+, S-100+, T4+, HLA-DR+, and showed the same variety of surface receptors detected in H-X cells; furthermore, in a case with massive infiltration of the paracortex by T6+ cells, lymph node LCs were faintly T11+ and some of the T6+ cells had lymphoid aspect. Our findings suggest that the H-X cell population of L-S disease is not homogeneous, but is composed of discrete cell subsets with distinctive antigenic and morphological traits closely resembling those of cells of LC lineage at different maturational stages.
Female↗
Immunohistochemical characterization of a B-cell signet ring cell lymphoma. Report of a case.
Signet ring cell lymphoma is a non-Hodgkin's lymphoma, characterized by neoplastic lymphoid signet ring cells very similar to epithelial mucin producing cells. We describe here a case of signet ring cell lymphoma in which the immunophenotypic markers of signet ring cells parallel those of plasma cells, being intensively T10+ (CD 38), weakly HLA-DR+, and To15 (CD 22) and T200 (CD 45) negative. The morphologic and immunohistochemical features of the case and the main differential diagnosis are preceded by a review of the literature.
B-Lymphocytes↗
Expression of HIV in lymph node cells of LAS patients. Immunohistology, in situ hybridization, and identification of target cells.
Monoclonal antibodies (MAb) anti-HIV core and envelope proteins and in situ hybridization, using cDNA HIV probe, were employed to determine which lymph node cells in LAS patients express viral antigens and viral nucleic acids. The results have been correlated with the histologic phases of LAS and with the germinal center lysis detected using DRC-1 MAb directed against follicular dendritic reticulum cells (FDRC). Viral antigens occasionally were detected on high endothelial cells of paracortical venules and frequently on germinal center FDR accessory cells; this last finding correlates well with the extent of FDRC lysis and of CD4+ and CD8+ lymphocyte infiltration in germinal centers. HIV replication, detected by in situ hybridization, was observed in mononucleated cells present in T and B areas and, in one case, in flat endothelium.
AIDS-Related Complex↗
Immunohistochemical heterogeneity of macrophage subpopulations in human lymphoid tissues.
The mononuclear phagocytic system is composed of cells which display a marked immunohistological heterogeneity. In the present study we have investigated the immunohistochemical and enzymatic features of macrophages and accessory cells present in human lymph nodes and spleen and, as control tissues, in thymus, liver, skin and heart. Our investigation has demonstrated that macrophages present in germinal centres display an immunophenotype different from that of macrophages populating T-dependent areas. Furthermore, cells lining lymph node sinuses and splenic sinusoids express endothelial and macrophage markers, and are able to modulate their immunophenotype according to different reactive conditions. These data suggest, on immunohistochemical grounds, that macrophages populating B- and T-dependent areas as well as sinuses of human peripheral lymphoid tissues, may modulate their immunophenotype according to environmental and antigenic influences.
B-Lymphocytes↗