bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lymphadenoma: a report of three cases of an uncommon salivary gland neoplasm
Authors: Ma J , Chan J K C , Chow C W , Orell S R 
Published: March 2003

Aims: Lymphadenoma of the salivary gland is a rare neoplasm that has not been properly characterized. This study describes the clinicopathological features of three cases.Methods and results: All three patients were males, ranging in age from 13 to 57 years. Two presented with a parotid mass, and one a preauricular mass. The tumours were well circumscribed, comprising anastomosing trabeculae, solid tubules, glands or basaloid islands of epithelium with or without cyst formation, accompanied by a prominent lymphoid stroma lacking sinuses. Large reactive lymphoid follicles were found in two cases. The epithelial cells were bland‐looking to mildly atypical. Immunostaining demonstrated dual luminal cell and abluminal basal cell differentiation, with the former being often subtle and highlighted only by immunostaining for epithelium membrane antigen or CAM 5.2, and the latter being highlighted by p63 immunostain.Conclusions: Although there is some variation in the histological pattern from case to case, lymphadenoma is a morphologically recognizable salivary gland adenoma characterized by a dense lymphoid infiltrate. Lack of familiarity with this tumour may lead to misdiagnosis as myoepithelial sialadenitis, lymphoma, metastatic carcinoma in lymph node or lymphoepithelial carcinoma.
In vitro treatment of human transforming growth factor‐β1‐treated monocyte‐derived dendritic cells with haptens can induce the phenotypic and functional changes similar to epidermal Langerhans cells in the initiation phase of allergic contact sensitivity reaction
Authors: Aiba S. , Manome H. , Yoshino Y. , Tagami H. 
Published: March 2003

SummaryHuman monocyte‐derived dendritic cells (MoDCs) obtained from peripheral blood monocytes (PBMC) cultured with granulocyte–macrophage colony‐stimulating factor (GM‐CSF) and interleukin‐4 (IL‐4) can be activated in vitro by a variety of simple chemicals such as haptens and several metals. Recently, it has been demonstrated that transforming growth factor‐β1 (TGF‐β1) can induce further differentiation of MoDCs to the cells that share some characteristics with epidermal Langerhans cells, i.e. they contain Birbeck granules and express E‐cadherin. In this study, using such TGF‐β1‐treated dendritic cells (TGF‐β1+ DCs), we examined the in vitro effects of representative haptens, i.e. NiCl2 and dinitrochlorobenzene (DNCB), on their phenotypic and functional characteristics, comparing with those reported in vivo in epidermal Langerhans cells during the sensitization phase of a contact sensitivity reaction. Treatment of TGF‐β1+ DCs with NiCl2 increased their expression of the molecules related to antigen presentation such as CD86, major histocompatibility complex class I and class II, and CD83, although weakly, in addition to that of those essential for their migration to the regional lymph nodes, such as CD49e, CD44 and its variant 6, while it down‐regulated the expression of the molecules required for homing to the skin and staying in the epidermis, such as cutaneous leucocyte antigen (CLA) and E‐cadherin. It also increased the production of tumour necrosis factor‐α, but not that of IL‐1β or IL‐12. DNCB also increased their CD86 expression and down‐regulated E‐cadherin and CLA, but did not affect other phenotypic changes that were observed in TGF‐β1+ DCs treated with NiCl2. TGF‐β1+ DCs treated with either NiCl2 or DNCB increased their allogeneic T‐cell stimulatory function. In addition, reverse transcribed polymerase chain reaction revealed augmented expression of chemokine receptor 7 mRNA by TGF‐β1+ DCs when treated with either NiCl2 or DNCB. Moreover, consistent with this data, TGF‐β1+ DCs treated with these chemicals chemotactically responded to macrophage inflammatory protein‐3β. These data suggest the possibility that TGF‐β1+ DCs present a good in vitro model to study the biology of epidermal Langerhans cells.
Adherent dendritic cells expressing high levels of interleukin‐10 and low levels of interleukin‐12 induce antigen‐specific tolerance to experimental autoimmune encephalomyelitis
Authors: Yang J.‐S. , Xu L.‐Y. , Huang Y.‐M. , Van Der Meide P. H. , Link H. , Xiao B.‐G. 
Published: March 2003

SummaryWe have previously shown that tolerance can be induced against acute experimental autoimmune encephalomyelitis (EAE) in Lewis rats by bone marrow‐derived dendritic cells (DC) that have been pulsed in vitro with encephalitogenic myelin basic protein peptide 68–86 (MBP 68–86), and injected subcutaneously into healthy rats prior to immunization with MBP 68–86 plus complete Freund's adjuvant. To elucidate better the properties of tolerogenic DC, we here compared plastic‐adherent DC with floating, non‐adherent DC, which were cultured for 7 days in the presence of granulocyte–macrophage colony‐stimulating factor plus interleukin‐4 (IL‐4). Adherent DC expressed high levels of IL‐10 mRNA and protein, and low levels of IL‐12 mRNA and showed high expression of CD54 compared with floating DC. Proliferation, nitrite concentration and capacity for antigen presentation were lower in adherent DC than in floating DC. There were no differences between adherent and floating DC regarding expression of CD11c, OX62, major histocompatibility complex class II, CD80, or CD86. Most importantly, we observed that adherent DC induced tolerance to EAE in vivo when injected subcutaneously into Lewis rats prior to immunization, while floating DC did not. Adherent DC‐mediated tolerance to EAE was associated with augmented proliferation, nitric oxide production and frequency of apoptotic cells as well as with up‐regulation of transforming growth factor‐β (TGF‐β) ‐expressing cells in T‐cell areas of lymph nodes. Tolerance induction by adherent DC seems to be related to a nitric oxide–apoptosis pathway and to up‐regulation of TGF‐β‐expressing cells.
Molecular signals and genetic reprogramming in peripheral T‐cell differentiation
Authors: Noble A. 
Published: March 2003

SUMMARYRearrangement of gene segments occurs in T lymphocytes during thymic development as the T‐cell receptor (TCR) is first expressed, allowing T cells to become central regulators of antigen specificity in the acquired immune system. However, further development of T cells occurs after population of peripheral lymphoid tissues, which can result in T‐cell expansion and differentiation into effectors of various immune function, or progression to memory T cells, anergic cells or death by apoptosis. This review focuses on more recent developments concerning the choices that peripheral T cells make between first encountering antigen through TCR recognition and death. These decisions are associated with a process of genetic reprogramming that alters the behaviour of cells so that immune responses are appropriately regulated.
Complement‐mediated lipopolysaccharide release and outer membrane damage in Escherichia coli J5: requirement for C9
Authors: O'Hara A. M. , Moran A. P. , Würzner R. , Orren A. 
Published: March 2003

SummaryLipopolysaccharides (LPS) are major antigenic components of the outer membrane of Gram‐negative bacteria and can stimulate activation of the complement system. Such activation leads to formation of the complement membrane attack complex (MAC) on the cell walls, LPS release and, in serum‐sensitive strains, to cell death. In this study, Escherichia coli J5 strains, which incorporate exogenous galactose exclusively into LPS, were used to generate target strains with different LPS chemotypes, and the LPS of the strains was labelled with tritium (3H‐LPS). The ability of normal human serum (NHS) and human complement‐deficient sera to release LPS was subsequently monitored. NHS‐induced release of 64–95·7% of 3H‐LPS within 30 min; overall, no significant difference was observed between release of LPS from E. coli J5 strains with different LPS chemotypes. In functional assays, maximum LPS release had occurred by 30 min and before maximum bacterial killing. Electron microscopy revealed NHS‐induced outer‐membrane disruption in the form of blebs at 15 min; at this time‐point the inner membrane remained intact. Background LPS release and no bactericidal activity were detected in heat‐inactivated serum or human sera deficient in C6, C7 or C8. The C9‐deficient (C9D) serum had low bactericidal activity and failed to induce LPS release; however, addition of purified human C9 reconstituted its ability to release LPS. This study demonstrated the need for functional C9 molecules for LPS‐releasing activities in serum‐sensitive E. coli J5 strains.
Neutralization of interferon‐γ in neonatal SOCS1−/− mice prevents fatty degeneration of the liver but not subsequent fatal inflammatory disease
Authors: Bullen Denise V. R. , Darwiche Rima , Metcalf Donald , Handman Emanuela , Alexander Warren S. 
Published: March 2003

SummaryMice lacking the suppressor of cytokine signalling‐1 (SOCS1) die within weeks of birth with extensive fatty degeneration of the liver, consistent with acute hepatic toxicity to interferon‐γ (IFN‐γ), and inflammation of multiple organs. We show here that treatment for 1 week from birth with neutralizing antibody to IFN‐γ rescues SOCS1−/− mice from lethal liver disease but the mice subsequently succumb to chronic inflammatory lesions characterized by T‐lymphocyte infiltration of skeletal muscle, pancreas, lung, liver and skin. Elevated blood levels of eosinophils, neutrophils and platelets were also observed and the thymic lymphocyte population was depleted of CD4+ CD8+ T cells and showed a reduced CD4 : CD8 ratio. All T‐cell populations in thymus, spleen and lymph node exhibited an increased proportion of cells bearing the activation marker CD44. These data suggest an important role for SOCS1 in T‐lymphocyte regulation.
The lipopolysaccharide co‐receptor CD14 is present and functional in seminal plasma and expressed on spermatozoa
Authors: Harris Claire L. , Vigar Miriam A. , Rey Nores Julia E. , Horejsi Vaclav , Labeta Mario O. , Morgan B. Paul 
Published: March 2003

SummaryCD14 is a 54 000‐molecular weight (MW) glycolipid‐anchored membrane glycoprotein, expressed on myeloid cells, which functions as a member of the lipopolysaccharide (LPS) receptor complex. Soluble forms of CD14 have been reported in plasma, cerebrospinal fluid, amniotic fluid and breast milk. In plasma and breast milk, soluble CD14 has been implicated as a regulator of T‐ and B‐cell activation and function. Expression of CD14 in the male reproductive system has not previously been investigated. We here show that soluble CD14 is present in seminal plasma at levels comparable to those in serum. Spermatozoa expressed CD14 on their membranes, as demonstrated by fluorescence microscopy and flow cytometry. Post‐vasectomy, the levels of seminal plasma CD14 (spCD14) were much reduced, implying an origin distal to the point of transection of the vas deferens. Ultracentrifugation analyses demonstrated that spCD14 was not associated with lipid complexes, indicating that it lacks the glycolipid anchor. Purified spCD14 mediated activation by LPS of CD14‐negative cells. These findings suggest that CD14 may play a hitherto unexplored role in immune defence and cell activation in the male reproductive tract.
Contribution of conformational stability of hen lysozyme to induction of type 2 T‐helper immune responses
Authors: So Takanori , Ito Hiro‐O. , Hirata Masato , Ueda Tadashi , Imoto Taiji 
Published: March 2003

SummaryIt is important to identify characteristics that confer on proteins the potential to induce allergenic sensitization and allergenic disease. Protein allergens carry T‐cell epitopes that are capable of inducing a type 2 T helper (Th2) cell response. There is limited information regarding factors that govern the allergenicity of proteins. We previously reported that a decrease in the conformational stability of hen‐egg lysozyme (HEL) enhanced its capacity to activate HEL‐specific T cells owing to the increased susceptibility to intracellular antigen processing. To determine whether the conformational stability of HEL makes for a critical contribution to allergenic sensitization in vivo, we immunized BALB/c mice with HEL derivatives of different conformational stability, but which retained a similar three‐dimensional structure. The magnitude of in vivo T‐cell responses, evaluated by ex vivo proliferative responses of lymph node T cells from mice primed with various HEL derivatives, was inversely correlated with conformational stability, as was interferon‐γ (IFN‐γ) and interleukin‐4 (IL‐4) production by splenic T cells in response to HEL. Immunization of the least stable derivative led to a potent IL‐4 response and to immunoglobulin E (IgE) antibody production. We propose that the intrinsic allergenicity of proteins can be determined by the degree of conformational stability.
Immune privilege and FasL: two ways to inactivate effector cytotoxic T lymphocytes by FasL‐expressing cells
Authors: Li Jie‐Hui , Rosen Dalia , Sondel Paul , Berke Gideon 
Published: March 2003

SummaryThe theory that Fas ligand (FasL)‐expressing tumours are immune‐privileged and can directly counterattack Fas‐expressing effector T lymphocytes has recently been questioned and several alternative mechanisms have been proposed. To address this controversial issue, we analysed the impact of FasL‐expressing tumours on in vivo‐primed cytotoxic T lymphocytes (CTLs) and the mechanisms involved. CTLs were obtained from the peritoneal cavity (PEL) after in vivo priming with syngeneic or allogeneic murine tumour cells. We have found that PEL populations undergo Fas‐based apoptotic cell death when co‐cultured with FasL‐expressing tumour cells and that PEL destruction of cognate targets in a 51Cr‐release assay was markedly inhibited by the pre‐exposure to either cognate or non‐cognate tumour cells expressing FasL. Furthermore, cytocidal function of PEL was markedly inhibited by preincubation with FasL‐negative tumour cells, if and only if they were the cognate targets of the CTL; this CTL inhibition involved FasL–Fas interactions. The killing function of ‘bystander’ PELs, reactive to a third‐party target cell, was inhibited by co‐cultivation with PELs mixed with their cognate target. This activation‐induced CTL fratricide was not influenced by the expression of FasL on the cognate target cells. These studies demonstrate the existence of two distinct pathways whereby FasL‐expressing cells inhibit in vivo‐primed FasL‐ and Fas‐expressing CTLs: first, by FasL‐based direct tumour counterattack, and second, by FasL‐mediated activation‐induced cell death of the CTLs, which is consistent with the concept that FasL expression in vivo could play a role in inducing immune privilege.
Glycoprotein B from strain 17 of herpes simplex virus type I contains an invariant chain homologous sequence that binds to MHC class II molecules
Authors: Sievers Elisabeth , Neumann Jürgen , Raftery Martin , SchÖnrich Günther , Eis‐Hübinger Anna Maria , Koch Norbert 
Published: March 2003

SummaryMajor histocompatibility complex class I (MHCI) molecules are major targets of virus evasion strategies because they introduce antigens from the biosynthesis pathway into the antigen‐processing and presentation pathways for immune recognition by CD8+ T cells. Little is known about viral strategies that interfere with the MHC class II (MHCII) antigen presentation pathway. We identified a six amino acid sequence from type I herpes simplex virus (HSV‐1) glycoprotein B (gB) that is identical to a sequence of human leucocyte antigen D (HLA‐D) ‐associated invariant chain (Ii). In addition, this gB sequence is adjacent to a highly conserved HLA‐DR1 binding motif. Both viral sequences together resemble the class II binding site of human Ii, consisting of a MHCII groove binding segment and a promiscuous binding site. We cloned gB from HSV‐1 strain 17 and demonstrate association of the virus envelope protein to three HLA‐DR allotypes. With chimeric Ii/gB fusion proteins we identified gB sequences that mediate promiscuous or allotype‐specific binding to the HLA‐DR peptide‐binding domain. Mutation of two Lys residues in the viral segment of Ii/gB abolished promiscuous binding to HLA‐DR heterodimers. The result indicates promiscuous binding of the virus sequence to HLA‐DR molecules and suggests a potential for HSV‐1 to manipulate antigen processing and presentation.
Insufficient interleukin‐2 production from splenic CD4+ T cells causes impaired cell proliferation and early apoptosis in SAMP1, a strain of senescence‐accelerated mouse
Authors: Nishimura Yasumitsu , Hosokawa Tomohide , Hosono Masamichi , Baba Mitsuo , Hosokawa Masanori 
Published: March 2003

SummaryWe examined the proliferative and cytokine‐producing activities of CD4+ T cells from young mice of the senescence‐accelerated mouse strain SAMP1, which had shown markedly low T‐dependent antibody‐producing responses. When splenic T cells were cultured with concanavalin A (Con A), the percentage of CD4+ cells decreased earlier in SAMP1 than in C3H/He mice. At 40 hr of culture, the percentage of BrdU‐labelled proliferating CD4+ cells increased strongly in C3H/He, but only slightly in SAMP1. When purified CD4+ T cells were cultured with Con A, the percentage of 5‐bromo‐2′‐deoxyuridine (BrdU)‐labelled cells peaked at around 48 hr of culture in both strains, but decreased significantly at 64 hr in SAMP1. The production of interleukin (IL)‐2 but not IL‐4 or interferon‐γ (IFN‐γ) was significantly lower in SAMP1 than in C3H/He at 48 hr of culture. IL‐2 production was also markedly low in SAMP1, even under the stimulation of anti‐CD3 with anti‐CD28 antibodies. The frequency of cells producing IL‐2 was significantly lower in SAMP1 than in C3H/He at 6–24 hr of culture with Con A. The percentage of annexin‐positive and propidium iodide (PI)‐negative apoptotic cells was significantly higher in SAMP1 than in C3H/He at 96 hr of culture. Exogenous IL‐2 prevented the decrease in BrdU‐labelled cells and the increase in apoptotic cells in the SAMP1 cell culture. These results indicate that SAMP1 CD4+ T cells cannot produce IL‐2 at levels sufficient to support cell proliferation and survival. This may account for the weak T‐dependent antibody response in SAMP1 mice.
A blood‐borne antigen induces rapid T–B cell contact: a potential mechanism for tolerance induction
Authors: Gütgemann Ines , Darling Jama M. , Greenberg Harry B. , Davis Mark M. , Chien Yueh‐Hsiu 
Published: March 2003

SummaryUnderstanding the difference between the development of a productive T‐cell response and tolerance is central to discerning how the immune system functions. Intravenous injection of soluble protein is thought to mimic the presentation of self‐serum and orally introduced antigens. It is generally toleragenic. The current view is that this outcome reflects the failure of ‘immunogenic’ dendritic cells to relocate to the T‐cell zone of the secondary lymphoid tissues. Here, using a peptide/I‐Ek tetramer and antibodies to stain splenic sections, we showed that antigen‐specific T cells were activated in the spleen within hours of injection or feeding of protein. The activated T cells were found to be located at the T–B junction, the bridging zone and the B‐cell area, interacting directly with B cells. In addition, B cells gain the ability to present antigen. Our results suggest a way for T cells to be stimulated by blood‐borne antigen presented by naïve B cells, a potential mechanism of tolerance induction.
γδ T cells contribute to the systemic immunoglobulin E response and local B‐cell reactivity in allergic eosinophilic airway inflammation
Authors: Svensson Linda , Lilliehöök Bo , Larsson Roland , Bucht Anders 
Published: March 2003

SummaryAllergic airway inflammation induced in mice is T‐cell dependent and recruitment of eosinophils to airspaces requires both αβ and γδ T cells. From previous studies it is evident that αβ T cells are essential for the allergic T helper type 2 (Th2)‐like response, while the mechanistic contribution of γδ T cells is still unclear. In this study, we have investigated the role of γδ T cells in allergic airway eosinophilia induced by ovalbumin hypersensitivity. By comparing the responsiveness to sensitizing allergen of wild‐type mice with that of T‐cell receptor γδ knockout mice (TCRγδ KO) we demonstrated that mice lacking γδ T cells are defective in the systemic ovalbumin‐specific immunoglobulin E (IgE) response. Furthermore, after aerosol challenge with allergen, γδ T‐cell deficient mice exhibited a significantly decreased migration of B cells and natural killer cells to airways and reduced levels of allergen‐specific IgG and IgA in bronchoalveolar lavage fluid. The role for B cells in the airway inflammation was indicated by the impaired ability of mice lacking functional B cells to evoke an eosinophilic response. The diminished eosinophilia in TCRγδ KO mice could not be explained by a defective Th2 activation since these mice displayed a normal IgG response in serum and an unaffected IG2b/IgG1 ratio in airways. Analysis of immunoregulatory cytokines in isolated lung tissue, thoracic lymph nodes and spleen further supported the notion that these mice are able to evoke a sufficient activation of T helper cells and that γδ T cells are not required for maintaining the Th2 profile. These results indicate that γδ T cells contribute to allergic airway inflammation by pathways separate from classical Th2 immune activation.
Administration of exogenous interleukin‐18 and interleukin‐12 prevents the induction of oral tolerance
Authors: Eaton Alfred D. , Xu Damo , Garside Paul 
Published: March 2003

SummaryInterleukin‐18 (IL‐18), a pro‐inflammatory member of the IL‐1 family, has been associated with autoimmunity and allergic disease. This type of pathology is thought to be the result of a defect in immunological tolerance and is often observed in inflammatory disorders of the gut such as coeliac disease, Crohn's disease and ulcerative colitis. IL‐18 has been implicated in a number of mucosal immune disorders, where it synergizes with IL‐12 to induce the production of interferon‐γ (IFN‐γ). We have therefore investigated the effects of IL‐18 and IL‐12 administration on the induction of oral tolerance to ovalbumin. The suppression of specific Ig G2a production, delayed‐type hypersensitivity responses and IFN‐γ production by antigen‐specific T cells were all abrogated by the presence of exogenous IL‐12 and IL‐18, suggesting that oral tolerance was broken. The expression of the co‐stimulatory molecule CD80 on dendritic cells was also shown to be increased by this combination of cytokines. As dendritic cells are thought to be of major importance in the induction of tolerance, this suggests a mechanism by which tolerance to mucosal antigens may be broken in vivo.