To investigate the differential expression of various types of leukocyte common antigen (LCA) isoforms during development, we analyzed human fetal lymphoid organs, including the thymus, liver, spleen, and bone marrow from 14 weeks to 29 weeks of gestational age by immunohistochemical and flow cytometric methods. In fetal thymus, over 90% of thymocytes throughout the entire fetal life expressed CD45RO and CD45RB, while CD45RA was expressed only in less than 5% of thymocytes. This expression pattern of LCA isoforms was established by a gestational age of 14 weeks or earlier, and persisted throughout the fetal period. The tissue distribution was different from each isoform; CD45RO-positive thymocytes were found in both the cortex and medulla at the 14th week with low intensity, but was localized in the cortex with increasing fetal age. CD45RB-positive thymocytes distributed mainly in the medulla from early gestational age. Among extrathymic lymphoid organs, a small portion of lymphoid cells expressing leukocyte common antigens appeared first in the liver at 10-12 weeks of gestational age and was followed by a small number in the spleen and bone marrow by 13-15 weeks. All lymphoid cells in these extrathymic lymphoid organs at this stage were CD19+ B cells. The number of these CD19+ cells increased abruptly during the early period of mid-gestational age. The pattern of tissue distribution of each LCA isoform in the fetal liver and spleen correlated well with the patterns of quantitative analysis by flow cytometry. In summary we found that different LCA isoforms expressed in cell-type-specific pattern and showed different tissue distribution during the period of fetal development, and that LCA was the earliest antigen expressed by lymphocytes in the thymus and extrathymic lymphoid organs in our series.
Antigens, CD45/*analysis ; Bone Marrow/immunology ; Female ; Fetus/*immunology ; Flow Cytometry ; Human ; Immunoenzyme Techniques ; Liver/immunology ; Lymphoid Tissue/*immunology ; Pregnancy ; Spleen/immunology

The nomenclature "embryonic lymphoid tissue inducer (LTi) cell" reflects the fundamental role of the cell in secondary lymphoid tissue organization. In addition, it is equally important in primary lymphoid tissue development as it regulates central tolerance to self-antigens in the thymus. An adult LTi cell constitutively expresses two sets of tumor necrosis factor (TNF) family members, whereas its embryonic counterpart expresses only one. The first set is lymphotoxin (LT)alpha, LTbeta, and TNFalpha, which are essential for the secondary lymphoid organogenesis during embryogenesis and for maintaining an organized secondary lymphoid structure during adulthood. The second set is OX40- and CD30-ligands, which are critical for memory T cell generation. Adult LTi cells regulate adaptive immune responses by providing LTbetaR signals to stromal cells to maintain secondary lymphoid tissue structure, and determine adaptive immune responses by providing OX40 and CD30 survival signals to activated T cells in memory T cell generation. Along with the consideration of the roles of embryonic LTi cells in primary and secondary lymphoid tissues, this review highlights the roles of adult LTi cells in secondary lymphoid tissue function.
Adult ; Animals ; Humans ; Lymphoid Tissue/cytology/embryology/*immunology ; Lymphokines/immunology/metabolism ; T-Lymphocytes, Helper-Inducer/cytology/*immunology/metabolism ; Thymus Gland/cytology/embryology/*immunology

Distribution and characterization of interlukin-10 (IL-10)-secreting cells in lymphoid tissues of pigs naturally infected with porcine circovirus type 2 (PCV2) were evaluated in accordance with PCV2 antigen detection. After screening a total of 56 pigs showing the symptoms of postweaning multisystemic wasting syndrome (PMWS), 15 pigs were PCV2 positive and 5 pigs, which showed stronger positive signals over multiples tissues were further investigated. This study showed that in PCV2-infected lymphoid tissues, particularly mandibular lymph node, spleen and tonsil, IL-10 expression was mainly localized in T-cell rich areas but rarely in B cell rich areas. IL-10 was highly expressed in bystander cells but rarely in PCV2-infected cells. Elevated IL-10 expression was predominantly associated with T cells, but rarely with B cells or with macrophages. The results of this study provide evidence for the role of IL-10 in chronic PCV2 infection and its relation to PCV2 antigen in affected tissues. Constantly elevated levels of IL-10 lead to immunosuppression in persistent and chronic viral infections. The increased IL-10 expression observed in PCV2 infection in this study suggests that IL-10-mediated immunosuppression may play an important role in the pathogenesis and maintenance of naturally occurring PCV2 infection.
Animals ; Circoviridae Infections/immunology/pathology/*veterinary ; Circovirus/*immunology ; Gene Expression Regulation/*immunology ; Immunohistochemistry/veterinary ; Interleukin-10/immunology/*secretion ; Lymphoid Tissue/immunology/*pathology/secretion ; Porcine Postweaning Multisystemic Wasting Syndrome/*immunology/pathology ; Republic of Korea ; Swine ; T-Lymphocytes/immunology

OBJECTIVETo evaluate the effect of the small intestinal mesenteric lymphoid tissues stimulating mixed lymphocyte reaction with dendritic cells (DC) and peripheral blood monocyte cells (PBMC), and observe the changes of the MHC molecular expression on DC.

METHODSDC, PBMC and mixed lymphocyte were separated to culture from SD rats. Lymphoid tissue suspension was adopted from small intestinal mesentery of Wistar rats. In the mixed lymphocyte reaction (MLR), the cellular proliferation of small intestinal mesenteric lymphoid tissue antigen act on DC and PBMC was detected with cell counting of CCK-8 assay, the same assay used in small intestinal mesenteric lymphoid tissue antigen and ovalbumin (OVA) acting on DC. FACS analysis was performed after lymphoid tissue suspension stimulating DC to observe the MHC molecular expression.

RESULTSIn the lymphoid tissue suspension, 91% of the cells was lymphocyte, others including granulocyte, plasmocyte, epithelium. The effect of stimulating mixed lymphocyte proliferation were higher in DC groups than in PBMC groups with the small intestinal mesenteric lymphoid tissue (P < 0.05). In the proportion of DC and mixed lymphocyte >or= 1:100 groups, the mixed lymphocyte proliferation were higher in the small intestinal mesenteric lymphoid tissues groups than in the OVA groups (P < 0.05). After stimulated by the small intestinal mesenteric lymphoid tissue, DC expressed higher MHC-I and -II molecules than control groups.

CONCLUSIONSThe small intestinal mesenteric lymphoid tissue has high antigenicity; the antigen presenting ability of DC was much stronger than granulocytes; DC expresses high MHC-I and MHC-II molecules after stimulated by mixed lymphoid tissue suspension.

Animals ; Cell Proliferation ; Cells, Cultured ; Dendritic Cells ; cytology ; immunology ; metabolism ; Flow Cytometry ; Intestine, Small ; immunology ; Lymphocyte Activation ; Lymphocyte Culture Test, Mixed ; Lymphoid Tissue ; cytology ; immunology ; Mesentery ; immunology ; Monocytes ; cytology ; immunology ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Sincalide ; analysis

Primary thymic marginal zone B-cell lymphoma (MZBL) of mucosa-associated lymphoid tissue (MALT)-type is a very rare disease with distinct clinicopathologic features. I herein report a rare case of primary thymic MZBL of MALT-type arising in the thymus in a patient with Sjogren's syndrome and rheumatoid arthritis. A mediastinal mass was detected by computerized tomography in a 43-yr-old Korean woman with a history of Sjogren's syndrome and rheumatoid arthritis and the thymus was resected through median sternotomy. The solid and nodular tumor (7x6x3cm) was confined in the thymus. Histologically, the lymphoid infiltrate comprised monotonous centrocyte-like cells with monocytoid cells, small lymphocytes, and plasma cells. Prominent lymphoepithelial lesions were formed by centrocyte-like cells infiltrating the Hassall's corpuscles. Immunohistochemically, the tumor cells were positive for CD20, CD79a, and bcl-2 and negative for CD3, CD5, CD10, CD23, and bcl-6. IgA and kappa light chain restriction were also found in plasma cells in the tumor. Sjogren's syndrome and rheumatoid arthritis are known to be associated with MALT lymphoma and were considered to play an important role in the development of malignant lymphoma in this patient.
Adult ; Arthritis, Rheumatoid/*complications/immunology ; B-Lymphocytes/metabolism ; Female ; Human ; Lymphoma, Mucosa-Associated Lymphoid Tissue/diagnosis/*etiology/immunology ; Sjogren's Syndrome/*complications/immunology ; Thymus Neoplasms/immunology/*pathology ; Tumor Markers, Biological

OBJECTIVETo investigate the expression of mucosal addressin cell adhesion molecule-1(MAdCAM-1) during small bowel graft rejection and the effects of MAdCAM-1 on the development of acute rejection.

METHODSRat heterotopic small bowel transplantation (SBT) was performed in F344/N rats with syngeneic and allogeneic (BN-F344/N) grafts. Bowel and gut-associated lymphoid tissue(GALT) samples were collected from small bowel transplants on postoperative day(POD) 1, 3, 5 and 7. Histopathology assessment of the grafts was conducted to identify the rejection. MAdCAM-1 was detected by immunohistochemistry and Western blot.

RESULTSDuring acute rejection, MAdCAM-1 was highly-expressed on gut lamina propia and GALTs, particularly on vascular endothelial cells in the gut lamina propia. There were no change of MAdCAM-1 expression in syngeneic grafts from POD1 to POD7. In allogeneic grafts, MAdCAM-1 expression in mesenteric lymph nodes was down-regulated, while up-regulated on the vascular endothelial cells in the lamina propria during acute rejection.

CONCLUSIONAlteration of MAdCAM-1 expression may be associated with the development of SBT graft rejection.

Animals ; Graft Rejection ; immunology ; metabolism ; Graft Survival ; Immunoglobulins ; metabolism ; Intestinal Mucosa ; immunology ; Intestine, Small ; transplantation ; Lymph Nodes ; metabolism ; Lymphoid Tissue ; Male ; Mucoproteins ; metabolism ; Rats ; Rats, Inbred BN ; Rats, Inbred F344

Six 1-month-old piglets were intravenously injected with deoxynivalenol (DON) at the concentration of 1 mg/kg body weight, with three pigs each necropsied at 6 and 24 h post-injection (PI) for investigation of hepatotoxicity and immunotoxicity with special attention to apoptotic changes and cytokine mRNA expression. Histopathological examination of the DON-injected pigs revealed systemic apoptosis of lymphocytes in lymphoid tissues and hepatocytes. Apoptosis of lymphocytes and hepatocytes was confirmed by the TdT-mediated dUTP-biotin nick end-labeling (TUNEL) method and immunohistochemical staining against single-stranded DNA and cleaved caspase-3. The number of TUNEL-positive cells in the thymus and Peyer's patches of the ileum was increased at 24 h PI compared to 6 h PI, but the peak was at 6 h PI in the liver. The mRNA expression of interleukin (IL)-1beta, IL-6, IL-18, and tumor necrosis factor (TNF)-alpha in the spleen, thymus and mesenteric lymph nodes were determined by semi-quantitative RT-PCR, and elevated expression of IL-1beta mRNA at 6 h PI and a decrease of IL-18 mRNA at 24 h PI were observed in the spleen. IL-1beta and IL-6 mRNA expressions increased significantly at 6 h PI in the thymus, but TNF-alpha decreased at 6 h PI in the mesenteric lymph nodes. These results show the apoptosis of hepatocytes suggesting the hepatotoxic potential of DON, in addition to an immunotoxic effect on the modulation of proinflammatory cytokine genes in lymphoid organs with extensive apoptosis of lymphocytes induced by acute exposure to DON in pigs.
Animals ; Apoptosis/*drug effects/immunology ; Cytokines/*biosynthesis/genetics ; Gene Expression Regulation/drug effects ; Histocytochemistry/veterinary ; In Situ Nick-End Labeling/veterinary ; Liver/*drug effects/immunology ; Lymphoid Tissue/*drug effects/immunology ; RNA, Messenger/*biosynthesis/genetics/immunology ; Reverse Transcriptase Polymerase Chain Reaction/veterinary ; Specific Pathogen-Free Organisms ; Swine/*immunology ; Trichothecenes/*toxicity

A high incidence of a T cell phenotype of sinonasal lymphomas in other Asian countries has been associated with a high incidence of Epstein Barr virus (EBV) infection. We analyzed 13 sinonasal and 18 Waldeyer's ring lymphomas for the prevalence of EBV encoded RNA (EBER) using a sensitive and specific in situ hybridization. In addition, we examined the relationship of histologic findings and immunophenotype as well as the location of the lymphomas to the presence of EBV. The EBER was detected in each of 12 sinonasal lymphomas with a T cell immunophenotype. One B cell sinonasal lymphoma was EBER negative. Four of 18 Waldeyer's ring lymphomas were positive for EBER, including two T cell lymphomas. Two of 16 B cell Waldeyer's ring lymphomas were EBER positive. Morphologically, 11 of 20 diffuse large cell lymphomas, 2 diffuse mixed small and large cell lymphomas, 2 of 4 immunoblastic lymphomas and 1 lymphoplasmacytic lymphoma were EBER positive. Four follicular large cell lymphomas were EBER negative. A characteristic angiocentric or angiodestructive pattern was found in most T cell lymphomas and EBER positive cases. These findings indicate that EBV infection is more strongly associated with the T cell immunophenotype, angiocentric pattern and sinonasal location of the lymphoma.
Adult ; Aged ; B-Lymphocytes/immunology ; Female ; Herpesviridae Infections/*virology ; Herpesvirus 4, Human/genetics/*isolation & purification ; Human ; Immunophenotyping ; In Situ Hybridization ; Incidence ; Lymphoid Tissue/virology ; Lymphoma, Non-Hodgkin/epidemiology/immunology/mortality/*virology ; Male ; Maxillary Neoplasms/epidemiology/immunology/mortality/*virology ; Middle Age ; Nasopharyngeal Neoplasms/epidemiology/immunology/mortality/*virology ; Nose Neoplasms/epidemiology/immunology/mortality/*virology ; Prevalence ; RNA, Viral/*analysis ; Support, Non-U.S. Gov't ; Survival Rate ; T-Lymphocytes/immunology ; Tonsillar Neoplasms/epidemiology/immunology/mortality/*virology ; Tumor Virus Infections/*virology

Germanium biotite (GB) is an aluminosilicate mineral containing 36 ppm germanium. The present study was conducted to better understand the effects of GB on immune responses in a mouse model, and to demonstrate the clearance effects of this mineral against Porcine reproductive and respiratory syndrome virus (PRRSV) in experimentally infected pigs as an initial step towards the development of a feed supplement that would promote immune activity and help prevent diseases. In the mouse model, dietary supplementation with GB enhanced concanavalin A (ConA)-induced lymphocyte proliferation and increased the percentage of CD3+CD8+ T lymphocytes. In pigs experimentally infected with PRRSV, viral titers in lungs and lymphoid tissues from the GB-fed group were significantly decreased compared to those of the control group 12 days post-infection. Corresponding histopathological analyses demonstrated that GB-fed pigs displayed less severe pathological changes associated with PRRSV infection compared to the control group, indicating that GB promotes PRRSV clearance. These antiviral effects in pigs may be related to the ability of GB to increase CD3+CD8+ T lymphocyte production observed in the mice. Hence, this mineral may be an effective feed supplement for increasing immune activity and preventing disease.
Aluminum Silicates/administration & dosage/*therapeutic use ; Animal Feed/analysis ; Animals ; Antigens, CD3/metabolism ; Antigens, CD8/metabolism ; Antiviral Agents/administration & dosage/*therapeutic use ; Concanavalin A/metabolism ; Dietary Supplements/analysis ; Disease Models, Animal ; Ferrous Compounds/administration & dosage/*therapeutic use ; Germanium/administration & dosage/*therapeutic use ; Lung/immunology/virology ; Lymphocyte Activation/drug effects ; Lymphocytes/cytology/drug effects ; Lymphoid Tissue/immunology/virology ; Mice ; Mitogens/metabolism ; Porcine Reproductive and Respiratory Syndrome/*drug therapy/pathology/virology ; Porcine respiratory and reproductive syndrome virus/*drug effects ; Swine