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Background Nasopharynx-associated lymphoid tissue ( NALT) serves as an important inductive site for mucosal immunity in the upper respiratory tract. Despite its importance in the mucosal immune system, little is known regarding the role of NALT in airway allergic immune responses. We aimed to elucidate the role of NALT in the induction of upper airway allergic responses in a mouse model. Methods Inhibitor of DNA binding/differentiation 2 ( Id2)−/− and Id2+/− mice was exposed to the ovalbumin ( OVA)-induced allergic rhinitis model, because the former resulted in the NALT deficiency. The allergic parameters, such as allergic symptoms, serum OVA-specific immunoglobulin E ( Ig E) levels, eosinophil infiltration, and cytokine profiles in the nasal mucosa, were compared between Id2−/− and Id2+/− groups. Results NALT-null, Id2−/− mice displayed significantly lower allergic responses compared with Id2+/− mice, as demonstrated by lower levels of allergic symptoms, serum OVA-specific Ig E, eosinophilic infiltration, and local Th2 cytokine transcriptions. To determine which of two factors, that is, the absence of NALT or the alteration of immunocompetent cell populations caused by the Id2 deficiency, has a larger effect on the attenuated allergic immune responses in Id2−/− mice, lethally irradiated Id2−/− mice were engrafted with C57 BL/6 wild-type bone marrow cells and showed still significantly lower allergic immune responses compared with equally treated Id2+/− mice. In addition, Ig E class switch recombination-associated molecules, such as ε immunoglobulin heavy-chain germline gene transcript, ε m RNA, and activation-induced cytidine deaminase m RNA, were detected in NALT from OVA-sensitized wild-type mice. Conclusion These results show the critical role of NALT for the induction of allergic responses in the upper airway at least in part by means of class switching to Ig E in situ. [ABSTRACT FROM AUTHOR]

The article focuses on a study conducted to investigate the use of liposomes for enhancing the ability of recombinant protein VP28, to fight the white spot disease (WSD) virus in kuruma shrimp. It reports the earlier studies done on the prevention and control of WSD, and discusses the benefits of strong biological reactivity of VP28. It also gives an overview of the experiments done during the study and explores their findings on the increase in survival rates of shrimps by liposomes use.

Isothermal oxidation of dense TiC ceramics, fabricated by hot-isostatic pressing at 1630°C and 195 MPa, was performed in Ar/O2 (dry oxidation), Ar/O2/H2O (wet oxidation), and Ar/H2O (H2O oxidation) at 900°–1200°C. The weight change measurements of the TiC specimen showed that the dry, wet, and H2O oxidation at 850°–1000°C is represented by a one-dimensional parabolic rate equation, while the oxidation in the three atmospheres at 1100° and 1200°C proceeds linearly. Cross-sectional observation showed that the dry oxidation produces a lamellar TiO2 scale consisting of many thin layers, about 5 μm thick, containing many pores and large cracks, while H2O-containing oxidation decreases pores in number and diminishes cracks in scales. Gas evolution of CO2 and H2 with weight change measurement was simultaneously followed by heating the TiC to 1400°C in the three atmospheres. Cracking in the TiO2 scale accompanied CO2 evolution, and the H2O-containing oxidation produced a small amount of H2. A piece of single crystal TiC was oxidized in 16O2/H218O to reveal the contribution of O from H2O to the oxidation of TiC by secondary ion mass spectrometry. [ABSTRACT FROM AUTHOR]

A new type of dual spin valve (DSV) structure with enhanced giant magnetoresistance (GMR) ratio is proposed, and the performance is characterized by the prototype read heads. The bottom part of DSV is kept as a synthetic pinned structure and only the top part adopts a monolayer pinned structure. The top monolaycr pin DSV (TM-DSV) showed three percentage points higher GMR ratio and 20% higher ΔR value. After the mechanical lapping process, the monolayer pinned layer can be stabilized by not only sense current but also large stress induced anisotropy due to Villari effect. After the quantitative analysis, the induced stress is measured to be about 4.2 x 109 N/m2. The bias point was tuned by adjustment of Cu spacer layer thickness using the RKKY interaction between pinned layer and free layer. There is no reliability concern related to the monolayer pinned structure. In a perpendicular magnetic recording system, TM.DSV technology could successfully demonstrate the output of 35.5 mV/μm and∼ 170 Gbits/in2 density feasibility. [ABSTRACT FROM AUTHOR]

The mucosal immune system acts as a first line of defense against bacterial and viral infections while also playing a crucial role in the establishment and maintenance of mucosal homeostasis between the host and the outside environment. In addition to epithelial cells and antigen-presenting cells (dendritic cells and macrophages), B and T lymphocytes form a dynamic mucosal network for the induction and regulation of secretory IgA (S-IgA) and cytotoxic T lymphocyte (CTL) responses. This review seeks to shed light on the pathways of induction and regulation of these responses and to elucidate the role they simultaneously play in fending off pathogen invasion and maintaining mucosal homeostasis. [ABSTRACT FROM AUTHOR]

SUMMARY The combination of allograft limbal transplantation (ALT) and amniotic membrane transplantation (AMT) has been applied in the treatment of severe ocular surface diseases. The beneficial effect of this combination has been thought to result from possible immunosuppressive ability of amniotic membrane (AM). However, the mechanisms of any such ability remain unknown. In this study, we investigated whether human AM has the ability to suppress allo-reactive T cell responses in vitro . For mixed lymphocyte reaction (MLR), lymphocytes isolated from lymph nodes of C57BL/6 mice (Mls1b , Vβ 6+ ) were cultured with irradiated splenocytes from DBA/2 mice (Mls1a , Vβ 6- ) with or without human AM. For carboxyfluorescein diacetate succinimidyl ester (CFSE) experiments, responder lymph node cells were labelled with a stable intracellular fluorescent dye and cultured with irradiated stimulator cells. The ratio of responder Vβ 6+ T cells was then determined by FACS analysis, and the division profiles of responder Vβ 6+ T cells were analysed by CFSE content. Furthermore, Th1 and Th2 cytokine synthesis by allo-reactive T cells in MLR culture supernatants was determined by enzyme-linked immunosorbent assay (ELISA). Addition of AM to the MLR culture resulted in the significant inhibition of thymidine incorporation compared with control culture lacking AM. The population of responder CD4+ Vβ 6+ T cells was significantly reduced in the AM-treated culture in comparison to control. CFSE analysis revealed less division and lower proliferation of responder CD4+ Vβ 6+ T cells in cultures with AM than without. In addition, allo-rective T cell synthesis of both Th1 (IL-2 and IFNγ) and Th2 (IL-6 and IL-10) type cytokine was significantly decreased in the presence of AM. These results indicate that human AM has the ability to suppress allo-reactive T cells in vitro . This inhibitory effect likely contributes to the success of the ALT-AMT combination. [ABSTRACT FROM AUTHOR]

The mucosal immune system is a first line of defense against foreign antigens, including microbial and dietary antigens. Under normal circumstances, the mucosal immune system employs tightly regulated dynamic mucosal intra- and internets consisting of inductive and effector sites for the induction of an appropriate immunological homeostasis between the host and mucosal environments. The common mucosal immune system (CMIS), which interconnects between inductive (e.g. Peyer patch) and effector (e.g. intestinal lamina propria) tissues for the induction of the IgA response, is well characterized. Recent results provide strong evidence for the presence of a CMIS-independent IgA induction pathway. Two distinct subsets of mucosal IgA-committed B cells termed B-1 and B-2, are associated with CMIS-independence and CMIS-dependent cascades respectively. In some cases, the breakdown of this tightly regulated mucosal immune system leads to pathological responses to different gut environmental antigens. As a result, disorders such as inflammatory bowel disease (e.g. IBD) and allergic gastroenteropathy can be evoked in the gastrointestinal tissues. Recently, many studies have described possible molecular and cellular mechanisms for this dysfunction in the gastrointestinal tissues by using murine models with specific gene manipulation. In this review we summarize recent findings from our group concerning the CMIS-dependent and CMIS-independent IgA induction pathways and gastrointestinal diseases (IBD and intestinal allergic diseases). These observations may provide useful information for the development of new mucosal immune therapy. [ABSTRACT FROM AUTHOR]

Cholera toxin (CT) and heat‐labile toxin (LT) of Escherichia coli act as adjuvants for the enhancement of mucosal and serum antibody (Ab) responses to mucosally co‐administered protein antigen (Ag). Both LT and CT induce B7‐2 expression on antigen‐presenting cells (APCs) for subsequent co‐stimulatory signalling to CD4+ T cells. CT directly affects CD4+ T cells activated via the TCR–CD3 complex with selective inhibition of Th1 responses whereas LT maintains Th1 cytokine responses with inhibition of interleukin (IL)‐4 production. Interestingly, while CT failed to induce mucosal adjuvant activity in the absence of IL‐4, LT did so. Nontoxic mutant (m)CTs (S61F and E112K) retain adjuvant properties by inducing CD4+ Th2 cells, which provided effective help for the Ag‐specific mucosal immunoglobulin (Ig)A, as well as serum IgG1, IgE and IgA Ab responses. The mCT E112K has been shown to exhibit two distinct mechanisms for its adjuvanticity. Firstly, mCT enhanced the B7‐2 expression of APCs. Secondly, this nontoxic CT derivative directly affected CD4+ T cells and selectively inhibited Th1 cytokine responses. Thus, several lines of evidence indicate that enzyme activity can be separated from adjuvant properties of CT and this offers promise for the development of safe delivery of vaccines for mucosal IgA responses. [ABSTRACT FROM AUTHOR]

In an in vitro study, Escherichia coli heat-labile toxin (LT) was shown to directly affect activated CD4(+) T cells and support interleukin (IL)-5 production in IL-4-deficient (IL-4(-/-)) mice, whereas cholera toxin (CT) did not. Both LT and CT enhanced B7-2 expression on B cells and macrophages. These effects were not influenced by CD40-CD40 ligand cosignaling. Addition of LT- or CT-treated antigen-presenting cells to anti-CD3-triggered CD4(+) T cells resulted in the induction of T cell proliferative responses. Further, these responses were inhibited by anti-B7-2 monoclonal antibody. Cocultivation of CD4(+) T cells with LT- or CT-treated antigen-presenting cells and anti-CD3 enhanced Th1- and IL-4-mediated Th2-type cytokine production. The results from in vitro studies were supported by in vivo studies in IL-4(-/-) mice, in which LT induced mucosal IgA responses but CT did not. Thus, although both LT and CT induce mucosal adjuvant responses via IL-4-dependent Th2-type responses, LT also elicits Th1- and IL-4-independent Th2-type responses. [ABSTRACT FROM AUTHOR]

Based upon the prosthodontic literature, subjects who are at the transition stage between natural dentition and edentulism are called "terminal dentition" (TD) cases. The aim of the present cross-sectional investigation was 10 characterize the local and systemic inflammatory responses in 2 groups of patients with terminal dentition periodontitis. Eight severe adult periodontitis terminal dentition (AP-TD) subjects and 8 early onset periodontitis terminal dentition (EOP-TD) subjects were entered into the study. Our purpose was to measure an extended battery of cytokines in the gingival crevicular fluid (CICE) and in lipopolysaccharide (LPS)-stimulated monocytic culture supernatants as well as gingival mononuclear cell messenger RNA (mRNA) transcripts determined from biopsy samples. Within the GCF there were 3 tiers (levels) of mediators based upon approximate 10-fold differences in concentration. The highest tier included prostaglandin E2 (PGE2), interleukin-1β (IL-1β) and interleukin-2 (IL-2), the intermediate tier included tumor necrosis factor alpha (TNFα) and interferon gamma (IFN-γ) and at the lowest concentration level were interleukin-4 (IL-4) and interleukin-6 (IL-6). Thus, the GCF analysis clearly indicated that in both AP-TD and EOP-TD groups the monocytic, i.e. IL-1β and PGE2 and Th1, i.e. IL-2 and IFN-γ, inflammatory mediator levels quantitatively dominated over the Th2 mediators, i.e. IL-4 and IL-6. LPS-stimulated monocytic release of IL-1β, PGE2 and TNFα was significantly elevated in both AP-TD and EOP-TD groups compared to those of a control group of 21 subjects with moderate to advanced adult periodontitis. The cytokine mRNA expression of isolated gingival mononuclear cells showed that in both the AP-TD and the EOP-TD groups Th1 and Th2 cytokines were expressed, with low levels of IL-4 and IL-12. In conclusion, our data suggest that this cross-sectional TD periodontitis model may reflect progressive periodontal disease associated with tooth loss. Furthermore, although Th1 cytokine levels in the GCF dominate over the Th2 response, monocytic activation provides the main source of proinflammatory mediators. In addition, LPS-stimulated peripheral blood monocytes demonstrate an upregulated inflammatory mediator secretion in the terminal dentition. [ABSTRACT FROM AUTHOR]

An accumulation of elevated numbers of macrophages (MΦ) and Ig producing cells is associated with localized and chronically inflamed gingiva of patients with adult periodontitis. When gingival lymphocytes were isolated from inflamed tissues and examined by flow cytometry, approximately 20-30% of lymphocytes were CD4+ T cells. For the analysis of Th1 and Th2 cytokine expression by these CD4+ T cells, RNA was extracted and reverse transcriptase polymerase chain reaction (RT-PCR) was performed by using specific 5' and 3' primers for IFN-γ and Il-2 (Th1), IL-4, IL-5, IL-6, IL-10 and IL-13 (Th2) and β-actin (housekeeping gene). Two distinct cytokine profiles were noted based on the expression of selected Th1 and Th2 cytokines. Thus, one pattern was represented by the expression of mRNA for IFN-γ, IL-6, IL-10 and IL-13, while the other case consisted of mRNA for IFN-γ , IL-6 and IL-13, Except for a few cases, messages for IL-2, IL-4 and IL-5 were not detected by cytokine-specific RT-PCR. The predominant expression of Th2 cytokines (e.g. IL-6, IL-I0 and IL-13) may contribute to the induction of high B cell responses in local disease sites. On the other hand, lack of IL-4 may be responsible for the accumulation of MΦ in diseased periodontium. We also investigated whether a relationship exists between IL-4 receptor (IL-4R) expression and MΦ persistence in the absence of exogenous IL-4. Gingival MΦ, when compared with monocytes ( MN ) MΦ from peripheral blood mononuclear cells (PBMC), expressed high levels of IL-4R mRNA. When gingival MΦ were incubated with recombinant IL-4(rIL-4), the cell viability was dramatically reduced by apoptosis. These findings clearly show that the lack of IL-4 may contribute to the persistant occurrence of MΦ at the disease site and addition of exogenous rIL-4 to gingival MΦ cultures leads to cell death by apoptosis. [ABSTRACT FROM AUTHOR]

Elevated numbers of plasma ceils are associated with localized and chronically inflamed gingiva of patients with adult periodontitis. However, only limited information is currently available as to how cytokines produced by CD4+ T cells are involved in these increased B cell responses in affected gingival tissues. When gingival mononuclear cells (GMC) were isolated from inflamed tissues and examined by flow cytometry. ∼20-30% of lymphocytes were CD4+ T cells. For the analysis of Th1 and Th2 cytokine expression by these CD4+ T cells. RNA was extracted and reverse transcriptase-polymerase chain reaction (RT-PCR) was performed by using specific 5' and 3' primers for interferon-gamma (IFN-γ)and IL-2 (Th1), lL-4, lL-5, IL-6, IL-10 and IL-13 (Th2) and β-actin (internal control). Two distinct cytokine profiles were noted based on the expression of selected Th1 and Th2 cytokines, where one pattern was represented by expression of mRNA for lFN-γ, IL-6, IL-10 and IL-13, white the second consisted of mRNA for IFN-γ, IL-6 and IL-13. In most samples, mRNA for IL-2, IL-4 and IL-5 were not detected by cytokine-specific RT-PCR. When RNA was isolated from CD4+ T cells of concanavalin A-stimulated peripheral blood mononuclear cells (PBMC) of the same patients and examined by RT-PCR, mRNA for all Th1 and Th2 cytokines were detected. These findings suggest that although human CD4+ T cells are capable of producing an array of Th1- and Th2-type cytokines, the CD4+ T cells associated with periodontitis are limited to production of IFN-γ, IL-6. IL-13 and in some instances IL-10. CD4+ T cells from diseased periodontal tissues are divisible into two groups based upon whether or not IL-10 is produced, together with IFN-γ, IL-6 and IL-13. [ABSTRACT FROM AUTHOR]

The humoral and genital secretory immune response to chronic SIV infection was compared between female Rhesus macaques inoculated by i.v, or intravaginal routes. Total IgG levels in serum were 10- fold higher in SIV-infected animals when compared with uninfected controls. Vaginal washes from normal macaques contained predominantly IgA and lgG. while those from SI V-infected animals contained high levels of IgG. The SIV-infected animals had high Litres of SIV-specific IgG in serum. with lower hut detectable IgA and IgM responses. The genital secretory immune response to SIV was similar in intravenously and intravaginally inoculated animals, The anti-SIV response in the vaginal washes consisted mainly of lgG. Within the lamina propria of the reproductive tract of animals chronically infected with SIV there were essentially no IgA or lgG plasma cells and only a small number of IgM plasma cells, while two normal animals had large number animales of IgA plasma cells. These results suggest that. the mucosal immune system of the female reproductive tract is impaired in chronic SIV infection. [ABSTRACT FROM AUTHOR]

Patients with adult periodontitis (AP) exhibit elevated serum antibody levels to Porphyromonas (Bacteroides) gingivalis; however, it is not known whether these antibodies originate from plasma cells in the local disease site or from peripheral lymphoid tissues. We studied the isotype and subclass levels and origin of antibodies to P. gingivalis fimbriae, since elevated serum anti-fimbriae responses were seen when compared with sera of healthy controls. IgG anti-fimbriae titres were dominant and the subclass response was IgG3 ≧ IgG1 > IgG2 ≧ IgG4; however, some IgA anti-fimbriae antibodies were also seen. The IgA subclass fimbriae-specific response was mainly IgA1: however, significant IgA2 anti-fimbrae antibodies were seen. We also assessed numbers of anti-fimbriae antibody producing cells from peripheral blood mononuclear cells (PMBC) and from either healthy or inflamed gingiva of AP subjects. Gingival mononuclear cells (GMC) of AP patients exhibited high numbers of immunoglobulin-producing (spot-forming) cells (SFC) including fimbriae-specific antibody secreting cells in a pattern of IgG > IgA > > > IgM, However, tow numbers of SFC were seen in GMC from healthy gingival further, no anti-fimbriae SFC responses were noted in healthy GMC. Although no fimbriae-specific immunoglobulin-producing cells were seen in PBMC, low numbers of antigen-specific SFC were found in pokeweed mitogen-triggered PBMC from AP subjects. Treatment of AP patients for plaque and surgical removal of inflamed gingiva resulted in significant reductions in serum anti-fimbriae responses. These studies show that AP patients exhibit brisk serum IgG and IgA subclass anti-fimbrtae antibodies, whose origin appear to be the plasma cells present in the localized inflamed tissues. [ABSTRACT FROM AUTHOR]

The level of serum IgM, IgG and IgA antibodies including IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2 subclass-specific antibodies to Bacteroides (Porphyromonas) gingivalis fimbriae and to lipopolysaccharide (LPS) were analysed in patients with different forms of periodontal disease (PD) and control subjects by ELISA. Among PD subjects, sera obtained from adult periodontitis (AP), rapidly progressive periodontitis (RPP) and gingivitis contained high titres of fimbriae-specific IgG antibodies (7500-15000 ELISA units) followed by IgA (90-700 units) and IgM (30-90 units). In contrast, sera from localized juvenile periodontitis (LJP) subjects exhibited much lower titres of (imbriae-specific IgG (89+11 units). IgA (31+5 units) and IgM (17+3 units) antibodies. A similar response pattern was also seen in sera from normal subjects aged 35-41 years who practice normal oral hygiene, while sera of younger adults (aged 18-24) with superior hygiene did not have any antigen-specific antibodies. Analysis of IgG subclass anti-fimbriae responses revealed that the major response was IgG3 followed by IgG1, IgG2 and IgG4 in AP, RPP and gingivitis. Although lower, a similar pattern of IgG subclass titre was seen in LJP and normal subjects aged 35 41 years. When IgA subclass responses were measured in AP and RPP. higher titres of the fimbriae-specific response were noted with IgA1 when compared with IgA2. However, lower but approximately equal levels of fimbriae-specific IgA1 and IgA2 titres were seen in other PD groups. When anti-B gingivalis LPS specific responses were measured, the sera of AP patients contained high levels of IgG antibodies (2265 ± 224 units) followed by IgA (411 ± 90 units) and IgM (214 ± 56 units). Further, IgG anti-LPS responses were mainly TgG2 followed by IgG4, IgG3 and IgGl. For IgA subclass responses, higher titres of anti-LPS-specific antibodies were noted in IgA2 subclass over IgA1. These results showed that higher anti-B, gingivalis antibody responses occur in PD when compared with healthy individuals and protein and lipid-carbohydrate antigens of B, gingivalis induce distinct patterns of antigen-specific IgG and IgA subclass responses. [ABSTRACT FROM AUTHOR]

The emergence of cells that produce IgG and IgA subclass antibodies to Bacteroides gingivalis (Porphyromonas gingivaiis) fimbriae and lipopolysaccharide (LPS) antigens was examined in mononuclear cells isolated from inflamed gingiva of different stages (slight, moderate or advanced) of adult periodontitis (AP). Antigen-specific IgM, IgG (including IgG1, IgG2, IgG3 and IgG4) and IgA (including IgAl and IgA2) producing cells were enumerated by the ELISPOT assay and were compared with total Ig-producing cells of each isotype or subclass. In advanced AP. the B. gingitalis fimbriae-specific IgG- and IgA-secreting cells represented 5% of total IgG- or IgA-secreting cells. while those from the moderate stage comprised approximately 1% of these two isotypes. Cells producing antibody specific for B. gingivalis LPS were observed at frequencies of 0.1% and 0.4% for IgG and IgA cells, respectively in the advanced stage. When IgG subclasses were analysed in moderate AP. the anti-fimbriae subclass responses were largely IgG1 (60%), followed by IgG2 (20%). lgG3(10%)and IgG4(10%), Fimbriae-specific IgG subclass responses were elevated in the advanced stage of AP, and IgG4 (40%) and IgG1 (30%) were dominant, followed by IgG3 (20%) and IgG2 (10%). IgA1 cells predominated in both the moderate and advanced stages, however a relative increase in IgA2 cells occurred in advanced AP, Mononuclear cells isolated from gingiva of AP patients did not contain cells producing antibody to antigens such as Fscherichia coli K235 LPS, cholera toxin or the hapten dinitrophenyl coupled lo bovine serum albumin. These results show that local IgG and IgA subclass responses occur to a protein antigen of a major periodontal disease (PD)- associated pathogen, B. gingivalis. and the increase in IgG4 and IgA2 responses may be associated with host protection. [ABSTRACT FROM AUTHOR]

Spontaneous adherence of bacteria to human peripheral blood mononuclear cells (PBMC) represents a useful tool for analysis of lymphocyte subsets with different functions. We have recently shown that PBMC can be divided into 2 populations based on their ability to bind Salmonella minnesota R345 (Rb) bacteria. By using these procedures, here, we provide evidence that Rb-bound and Rb-unbound PBMC populations give similar proliferative responses to phytohemagglutinin (PHA) and concanavalin A (Con A), while the pokeweed mitogen (PWM)-induced proliferative and differentiative responses are higher in the Rb-unbound than in the Rb-bound PBMC fraction. Moreover, enhanced PWM-induced responses are obtained in Rb-unbound cell cultures enriched for T4+ cells. When B (non-E rosetting) cells are cultured with purified T lymphocytes from the Rb-bound (T-Rb+) and Rb-unbound (T-Rb-) fractions, comparable PWM-induced mitogenic responses are observed, The T-Rb- population contains a higher percentage of cells expressing T4+ phenotype, and when added to B cell cultures a more elevated PWM-induced IgA, IgG and IgM synthesis is observed than in B cell cultures containing T-Rb+ cells. These results suggest that the T-Rb+ fraction is enriched for T cells which help IgA, IgG and IgM responses. [ABSTRACT FROM AUTHOR]

Murine T cells and T-cell lines express receptors for the Fc of IgA (Fc α R); however, their molecular properties remain to be elucidated. In the present study, we examined three candidate molecules for IgA-binding receptors including Fc α R, β-galactosyltransferase (β-GT) and anti-secretory component (SC) reactive proteins (ASCP) expressed on T cells which might participate in the binding of different molecular forms of IgA. T-cell lines derived from CD4+ T cells of mouse Peyer's patches (PP) (designated PPT 4-6 and PPT 4-16) and from cloned PP T helper (Th) cell lines (ThHA1 #9 and #10) bound both monomeric and dimeric IgA (mIgA and dIgA), while the fusion partners (BW 5147 and R1.1) did not. In contrast, both Fc α R+ and Fc α R- cell lines bound to high molecular weight polymeric or aggregated IgA (pIgA). All cell lines reacted with a monoclonal anti-β-GT (MoAb) and β-GT enzyme activity was associated with the cell lysates and membrane fractions of all cells tested. The anti-β-GT MoAb stained a 47-kDa band on immunoblots which was identical to that seen with native enzyme. mRNA analysis with β-GT cDNA showed that all cell lines constitutively produced enzyme-specific mRNA. Both Fc α R+ T cells and Fc α R- control cell lines showed cell surface specific β-GT activity. This is the first study which shows that mouse T cells produce β-GT. However, Fc α R and β-GT appear to be separate receptors, because Fc α R+ T cells bound mIgA and dIgA, and this treatment did not affect staining with biotinylated anti-β-GT MoAb. Further, preincubation of the Fc α R+ cells with anti-β-GT MoAb did not block mIgA binding. However, the anti-β-GT MoAb partially blocked binding of pIgA to both Fc α R+ and Fc α R- T cells, suggesting that β-GT may be a receptor for pIgA. Others have shown that T cells may bind IgA through a receptor serologically related to SC. We found that antibodies both to human SC and to rat SC specifically bound to both Fc α R+ and Fc α R- T cells. Further, a 72-kDa band was detected when cell membrane fractions were analysed with these antisera (ASCP) by solid phase immunoisolation technique and immunoblot analysis. The ASCP is not an IgA-binding receptor, since anti-SC did not block either mIgA or pIgA binding. Further, the effects of proteolytic enzymes were different on these three IGA-binding molecule candidates. Fc%alpha;R and ASCP were shown to be sensitive to pronase proteolytic degradation, but were resistant to trypsin and trypsin/EDTA treatements. In contrast, β-GT was sensitive to both pronase and trypsin treatements. We conclude that multiple IGA receptors are present on mouse T cells, and include those which bind to mIGA or dIgA (FcαR) as well as those wihich bind to pIgA (β-GT). Further, ASCP is also present on mouse T-cells lines, but its role in IgA binding to T cells remains to be further determined. [ABSTRACT FROM AUTHOR]

The induction of immune responses to orally administered trinitrophenyl (TNP)-haptenated Streptococcus mutans and its enhancement with muramyldipeptide (MOP), peptidoglycan (PG), and concanavalin A (Con A) were investigated in lipopolysaccharide (LPS)-non- responsive C3H/HeJ mice and the syngeneic, LPS-responsive C3H/HeN strain. Both mouse strains manifested similar immune responses, primarily of the IgM isotype, after a single gastric intubation (GI) with TNP-S. mutans. However, when groups of animals were first carrier-primed by GI with S. mutans for 2 consecutive days, followed by a single GI with TNP-S. mutans 1 week later, C3H/HeJ mice gave a significantly higher (P≤0.01) splenic IgA anti-TNP plaque-forming cell (PFC) response than identically treated C3H/HeN mice. Furthermore, saliva, urine and serum from these C3H/HeJ mice possessed high levels of IgA anti-TNP antibodies as determined by the enzyme-linked immunosorbent assay, whereas C3H/HeN mice exhibited low antibody levels. Oral administration of Con A (either 250 μg or 500 μg/mouse) or purified PG (1 mg/mouse) at the time of TNP-S. mutans immunization resulted in significantly (P≤0.01) enhanced splenic IgA anti-TNP PFC responses, especially in C3H/HeJ mice. On the other hand, MDP promoted lea anti-TNP PFC responses in LPS-responsive C3H/HeN mice but did not augment responses in C3H/HeJ animals. A similar immune response pattern was seen when antibody levels were measured in serum, saliva, and urine of both mouse strains. These results demonstrate that haptenated S. mutans is a good antigen for the induction of high IgA responses in orally immunized C3H/HeJ mice and that this high response can be enhanced with the adjuvants Con A and PG. However, MDP is ineffective in C3H/HeJ mice but enhances IgA responses in normal LPS-responsive C3H/HeN animals. [ABSTRACT FROM AUTHOR]

Immunofluorescent and esterase staining of Peyer's patch (PP) cell preparations from six mouse strains showed that each strain possessed approximately equal numbers of T and B cells but less than 1% esterase-positive cells (macrophages; Mφ). The addition of concanavalin A (Con A) to either lipopolysaccharide (LPS)-responsive C3H/HeN or LPS-nonresponsive C3H/HeJ PP cultures immunized with sheep erythrocytes (SRBC) resulted in good anti-SRBC plaque-forming cell responses, whereas the addition of Con A to PP cultures from SRBC orally primed C3H/HeJ mice resulted in significantly higher in vitro responses to trinitrophenyl-conjugated SRBC than similarly treated cultures from C3H/ HeN mice. On the other hand, muramyl dipeptide (MDP) promoted higher responses in PP cultures derived from either normal or carrier-primed LPS-responsive (C3H/HeN) mice than were observed with C3H/HeJ PP cultures. A similar pattern of responsiveness was seen when LPS prepared by a phenol-water extraction procedure (LPS(Ph)) was added to PP cultures. When LPS prepared by a butanol-water extraction method was used, PP cultures from both C3H/HeN and C3H HeJ mice were enhanced; however, the response of C3H/HeN PP cultures was significantly greater than that seen with C3H/HeJ PP cultures. The enhanced responsiveness of C3H/HeN PP cultures to MDP was probably due to an effect on the Mφ, since addition of MDP to either C3H/HeN or C3H/HeJ PP cultures containing C3H/HeN splenic adherent cells resulted in significantly enhanced immune responses. C3H/HeJ splenic Mφ did not promote adjuvant responses. LPS(Ph) augmentation of immune responses required that Mφ (spleen) and PP cultures be derived from LPS-responsive C3H/HeN mice. These results demonstrated that Con A, MDP, and LPS promoted immune responses of PP cultures to the T-dependent antigen, SRBC. Evidence is presented that Con A enhanced T-helper-cell activity, whereas MDP and LPS required the presence of LPS-responsive Mφ for augmentation of immune responses. [ABSTRACT FROM AUTHOR]

To determine if there is an association between the isotype of simian immunodeficiency virus (SIV)-specific B cell responses and the profile of Th1 and Th2 cytokine expression, rhesus macaques were immunized with SIV antigens via the iliac lymph nodes, using a targeted lymph node (TLN) immunization procedure. When CD4+ T cells purified from antigen-stimulated peripheral blood mononuclear cells were analyzed, the levels of Th2 cytokine production were gradually increased after the second and third immunizations. However, interferon-gamma production did not change. Analysis of SIV-specific B cell responses revealed that the main isotype was IgG after the second and third immunizations. In addition, a peak of SIV-specific IgA B cell responses was noted following the third immunization. These findings suggest that the induction of Th2 type responses in TLN-immunized rhesus macaques reflects the sequence of initial induction of SIV-specific IgG-producing cells followed by IgA-secreting cells. [ABSTRACT FROM AUTHOR]

Oral administration of large doses of protein antigen generally induces a state of systemic unresponsiveness currently termed mucosally induced tolerance. In this study, we used human milk protein (HMP) without casein as a multi-protein antigen for the study of mucosally induced tolerance. The HMP utilized in this study mainly contained secretory (S) IgA, lactoferrin (LO and a-lactalbumin (Lact). When mice were given 1 or 25 mg of HMP orally 3 times or 25 mg orally four consecutive weeks prior to systemic immunization, antigen-specific serum IgG responses to HMP were induced by subsequent parenteral immunization with 100 μg of HMP. Analysis of IgG subclasses revealed that IgG1 followed by IgG2b accounted for the IgG responses noted. When both HMP and ovalbumin (OVA) were fed to mice, tolerance developed to OVA but not to HMP. To further investigate the nature of immune responses seen following oral gavage of HMP, we examined responses to individual protein of HMP. Brisk serum IgG1 and IgG2b responses to both S-IgA and Lf were induced by oral followed by systemic immunization with HMP. Analysis of splenic CD4+ T cells from mice given oral HMP revealed production of Th2- but not Thl-type cytokines. These results show that oral administration of HMP preferentially induces exclusive Th2-type immune responses, which may prevent the development of HMP (S-IgA and Lf)-specific mucosally induced tolerance. [ABSTRACT FROM PUBLISHER]

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