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In this paper the phenomenon of suppression of proliferation in vitro of 14 day primed, West Nile Virus (WNV)-specific, murine CD4+ T cells by large numbers of antigen-presenting macrophages and B cells has been investigated. Suppression was apparently not mediated by prostaglandins, as the use of indomethacin in cultures at four times the usual concentration did not reverse suppression. Experiments were designed to evaluate the contribution of major histocompatibility complex (MHC) Class II and nominal WNV antigens in causing suppression of T cell proliferation. Listeria- or thioglycollate-induced macrophages from CBA/H (H-2k) mice, when treated with heat-killed Listeria in vitro for 1 h to maintain or increase, respectively, MHC Class II levels before the addition of alloreactive Iak-specific T cells caused inverse dose-responses; the highest T cell proliferation occurred at a stimulator to responder (S:R) ratio of 0.25 and profound suppression at a S:R ratio of 1 or 2. In contrast, untreated thioglycollate-induced macrophages, which express low MHC Class II levels, gave a direct dose-response with increasing T cell proliferation as antigen-presenting cell (APC) numbers increased. Addition of anti-Ia antibodies (or their Fab fragments) to cultures caused a significant reversal of suppression of anti-WNV T cells imposed by high numbers of Listeria-induced macrophages or 14 day WNV-primed B cell APC. Suppression was also reversed by reducing the concentration of WNV antigen. These observations support the notion that the suppression of T cell proliferation observed at high S:R ratios was due to high concentrations of ligand (WNV-derived peptide complexed with Class II MHC) on APC. [ABSTRACT FROM AUTHOR]

I am delighted to have been asked to join in the celebrations of Bob Blanden's scientific life. Though I have never formally collaborated with Bob, it has been a pleasure to interact with him on many occasions, and so it was particularly touching to be invited. I have always had a special regard for Bob as a gentleman scientist. Bob said in his email to me: ‘I would be most delighted if you could spend some time dealing with the importance of immunological theory in general, with particular attention to the genesis of your two signal model, and how it stands in the context of modern immunology.’ I am happy to respond to this request. The genesis of ideas, formally expressed in scientific papers, but normally in a manner that gives little insight into their origin, has always interested me. There is merit in formality and objectivity. However, it is also interesting to trace the origin of ideas, and to get a glimpse of the nature of the inspiration. [ABSTRACT FROM AUTHOR]

Keywords: CD8 T cell; immunosenescence; leishmania; NK cell; NKG2D; sestrin EN CD8 T cell immunosenescence leishmania NK cell NKG2D sestrin 431 433 3 07/03/20 20200701 NES 200701 In Covre I et al. i and Pereira I et al i ., the authors demonstrate the parallels between senescent NK cells and senescent CD8 T cells, and formalise the mechanism by which senescent CD8 T cells become more NK cell-like, through the action of sestrins. Given that these senescence features are shared across NK cells and CD8 SP + sp T cells and they emerge at the same time across these populations, it is very likely that a common mechanism could drive senescence in each cell type. Finally, while sestrins mediate senescence and NK cell-like functions in CD8 SP + sp T cell, the mechanism that underpins senescence in NK cells is unclear. [Extracted from the article]

The article discusses a study concerning Toxoplasma gondii, a tremendously well-evolved parasite, and can attack and infect any nucleated cell in the human body. According to the researchers, certain phagocytic cells can actively engulf parasites and limit acute infection. Researchers provide some definitive evidence of a previously explored hypothesis. Details and conclusion of the study are presented.

Although transforming growth factor-β (TGF-β) has been shown to positively regulate the development of murine T helper type 17 (Th17) cells, which of the intracellular signaling pathways are involved is controversial. We examined Smad-dependent and -independent signaling molecules downstream of the TGF-β receptor (TGFβR) involved in Th17 differentiation of naive murine CD4+CD62L+ T cells. During Th17 differentiation of wild-type T cells, Smad2/3 was phosphorylated, indicating activation of the canonical Smad pathway. T cells lacking TGFβRII did not differentiate into Th17, whereas T cells treated with a TGFβRI kinase inhibitor (SB-431542) or overexpression of inhibitory Smad7 retained a low amount of Th17 polarization despite absent Smad2/3 phosphorylation. Using protein antibody arrays we found an increase of expression and phosphorylation of the following Smad-independent signaling molecules in Th17-polarized wild-type T cells: AKT1(Tyr474), AKT2 (Ser474), ERK1-p44/42 MAPK(Tyr204), mTOR(Thr2446), p38 MAPK(Thr180), Rac1/cdc42(Ser71), SAPK/JNK(Tyr185) and SP1(Thr739). Pharmacological inhibition of AKT/mammalian target of rapamycin (mTOR) signaling with rapamycin or LY294002 decreased Th17 differentiation of wild-type T cells, and completely abolished interleukin-17 production in T cells with overexpression of Smad7. Rapamycin and LY294002 also decreased induced regulatory T cell differentiation, but only had minor additive effects to Smad7 overexpression. Finally, inhibitors of mitogen-activated protein kinase (MAPK) blocked in vitro polarization of Th17 cells. Our data show that Smad-dependent and -independent intracellular pathways contribute to murine Th17 differentiation. [ABSTRACT FROM AUTHOR]

The distribution and function of the C-type lectin Mincle has not previously been investigated in human cells, although mouse models have demonstrated a non-redundant role for Mincle in the host response to fungal infections. This study identified an unusual pattern of reciprocal expression of Mincle on peripheral blood monocytes or neutrophils isolated from the same donor. Expression on monocytes was inversely correlated with phagocytosis and yeast killing, but was necessary for the induction of inflammatory cytokines in response to ex vivo Candida challenge. In contrast, Mincle expression on neutrophils was associated with phagocytic and candidacidal potential of those cells. Candida challenge upregulated Mincle expression but only in Mincle+ cells. These data highlight species-specific differences between the regulation of Mincle expression in mouse and man. Reciprocal expression of Mincle modified the candidacidal potential of monocytes or neutrophils, suggesting it may also polarize the type of host response to fungal infection. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis, which is caused by Leishmania donovani, is one of the major health problems of the Indian subcontinent. Infected hosts have been reported to have impaired lymphoproliferation. However, the fate of anergic cells is still elusive. In the present investigation, L. donovani-infected hamsters were used to study the mechanism of lymphocyte cell death. Lymph node-derived lymphocytes were analysed for apoptotic death through mitochondrial abnormality, caspase activity and DNA degradation. The data demonstrate that the disease progression leads to a gradual impairment of lymphocyte proliferation in the presence of Concanavalin A. The fate of the anergic lymphocytes is intrinsic apoptosis, which is evident by the depolarization of the mitochondrial membrane potential, cytosolic release of cytochrome c, caspase activation and DNA fragmentation. Tumour growth factor (TGF)-β, which is secreted by macrophages, was significantly upregulated in the lymph node compartment of infected hamsters. Adding a neutralizing TGF-β antibody and a recombinant TGF-β resulted in the downregulation and induction of lymphocyte apoptosis, respectively. Furthermore, it has been observed that TGF-β triggers the apoptotic death of lymphocytes through the upregulation of tyrosine phosphatase activity and that the use of sodium orthovanadate (Na3VO4, a tyrosine phosphatase inhibitor) reduces the apoptotic frequency. Thus, this study clearly reports the novel involvement of tyrosine phosphatases in TGF-β-induced lymphocyte apoptosis in Leishmania-infected hamsters. [ABSTRACT FROM AUTHOR]

Dendritic cells (DC) are professional antigen-presenting cells with a unique T-cell stimulatory aptitude that play a crucial role in the instruction of adaptive immune responses upon infection. By controlling the initiation of a diverse set of effector functions, which are suitable for the elimination of a wide range of pathogens, DCs form the pivotal link between the innate and the adaptive immune system. The innate pattern recognition pathways that trigger DC activation are central for skewing of the adaptive immune responses that are subsequently induced. Thus innate activation not only precedes adaptive immune activation, it also controls it and tailors the effector functions to the requirements of the infection. The adaptive immune response has to match the nature of the infection, but this does not only concern the type of pathogen, it is also affected by the localization of the infection. Tissue homeostasis has to be ensured and thus tissue-derived environmental factors influence the functional activity of activated DCs and thereby contribute to shaping of the immune response. Adaptive immune responses are vital for the elimination of pathogens, have the potential to attack tumor cells and play a detrimental role during transplant rejection and in a variety of autoimmune diseases. Better understanding of the mechanisms that control the induction of different T-cell effector functions will enable the development of strategies to manipulate the immune system in the context of vaccination, tumor immunotherapy, transplantation and autoimmunity.Immunology and Cell Biology (2008) 86, 389–397; doi:10.1038/icb.2008.26; published online 1 April 2008 [ABSTRACT FROM AUTHOR]

The broadest definition of dendritic cells (DCs) is white blood cells that can take up antigen, process it and then present antigen-derived peptides to activate cognate naive T cells. Although this definition is by no means perfect, it is nevertheless now textbook. The source of frustration more recently has focused on other issues, including the distinction of the DC subtypes, their differential roles in the immune system, their lineage relationship to each other (and other leukocytes) and whether the mouse and human DC findings overlap. Here, I condense the classification of DCs in both the steady state versus infection, with primary focus in the mouse. Emphasis is then given to debates surrounding the in vivo pathways of DC differentiation in different conditions, which culture models best represent these processes (fms-like tyrosine kinase 3 ligand versus granulocyte-macrophage colony-stimulating factor), and what the human and mouse DC subtype equivalents might be. In addition, a model termed ‘graded’ commitment is proposed that, as a departure from the classic binary models of hematopoiesis, attempts to explain the recent clonal data where subtype-specific DC precursors branch from this pathway.Immunology and Cell Biology (2008) 86, 439–452; doi:10.1038/icb.2008.28; published online 15 April 2008 [ABSTRACT FROM AUTHOR]

On target cells, interleukin-6 (IL-6) interacts with its receptor complex consisting of the membrane-bound IL-6 receptor (IL-6R) and the signal transducing protein gp130. IL-6R can exist as a soluble protein (sIL-6R), which binds the ligand IL-6. This soluble complex can bind to gp130 on cells that lack the membrane-bound IL-6R and initiate signaling. This process is named transsignaling. The significance of transsignaling via sIL-6R is underlined by different publications and exceeds very probably the significance of the membrane-bound IL-6R. It is the general assumption that sIL-6R acts as an agonist in combination with IL-6 resulting in an enhancement of the IL-6 effects. In this article, we suppose ‘non-agonistic’ properties. There are several publications that give reasons to speculate that sIL-6R (a) has IL-6-antagonistic effects, (b) has orphan properties and (c) interacts with yet unknown binding partners different from IL-6. Knowledge about additional properties of sIL-6R will enlarge the biologic understanding of this molecule and might give an explanation for the sometimes contrasting effects of the cytokine IL-6.Immunology and Cell Biology (2008) 86, 87–91; doi:10.1038/sj.icb.7100113; published online 28 August 2007 [ABSTRACT FROM AUTHOR]

Cholera toxin (CT) has been reported to cause a variety of effects on several different cell types. Recently, CT has been shown to increase the susceptibility of ovarian carcinoma cells to cytotoxicity mediated by a variety of effector cells (natural killer, lymphokine-activated killer cells and tumour-associated lymphocytes derived from ascites of ovarian cancer patients) of both autologous and allogenic background. In the present study, CT demonstrated several effects on a newly established ovarian carcinoma line (SR8)1 when added to the culture medium at a concentration of 12.5 ng/mL for 2 days. Cholera toxin altered SR8 morphology to a uniform polygonal cellular shape, with less cell dispersion than the non-CT treated cells. Cholera toxin prolonged the population doubling time by approximately 10 h. The CT-treated SR8 cells exhibited reduced epidermal growth factor receptor expression (39 versus 50%), and increased carbohydrate antigen 125 expression (45 versus 2%) in both immunocytochemical and quantitative flow cytometric analyses. These changes in morphology and tumour marker expression were reversible when CT was removed from the culture. The CT-treated SR8 cells showed reduced capacity to generate tumours in female nude mice in comparison with non-CT treated cells, which produce both subcutaneous and intraperitoneal xenografts with local invasion in an animal model. Cytogenetic analysis of the cell line SR8 before and during treatment with CT showed no new clonal rearrangements. The possible mechanisms involved and the influence of CT on the biological behviour of ovarian tumour cells are discussed. [ABSTRACT FROM AUTHOR]

The article presents an abstract of the research paper "GST-P: A New Preneoplastic Marker During Mouse Hepatocarcinogenesis," by Xiao Yan He and R.C. Nicholson. The p class glutathione S-transferase (GST-P) is specifically and highly increased during rat hepatocarcinogenesis, and GST-P positive foci persist for a long time after a single dose of carcinogens such as diethylnitrosamine. This short-term mouse hepatocarcinogenesis study indicates that oval cells and transitional cells stain positive for GST-P in livers of diethylnitrosamine treated mice.

A model for cell movement is presented. It is suggested that cells do not migrate on collagen using their VLA (very late antigen) integrins that bind this extracellular matrix protein. Rather, the cells utilize αv integrins to bind endogenously produced fibronectin, which binds to the underlying collagen. It is envisaged that cells proceed by a process of engagement and disengagement of αv integrins to the extracellular matrix, somewhat analogous to the motion of a monkey climbing a tree. Secretion of isoforms of the adhesion modulator, thrombospondin, regulates disengagement of the integrin from its ligand in migrating cells. The integrin disengagement signal is mediated by thrombospondin cross-linking the αv integrin to an integrin accessory molecule and thus activating protein kinases. The cross-linked receptor complex undergoes recycling back along actin stress fibres, guided by the integrin P-subunit. After endocytosis and protein sorting the αv integrin is transported back to the leading edge off migrating cells in vesicles guided by the tubulin-binding capabilities of an integrin accessory molecule. Direct attachment to collagen required for processes, such as matrix contraction, is mediated by VLA integrins which displace αv integrins from points of attachment during integrin recycling, possibly through an αvβ1, intermediary receptor. [ABSTRACT FROM AUTHOR]

Bispecific antibody (BSAh) consisting of anti-CD3 plus anti-c-erbB-2 Fab fragments for the application to adoptive tumour immunotherapy was prepared. This bifunctional hetero-F(ab')2 antibody reacted with both human CD3+ T cells and c-erbB-2 positive human tumour cells. Human CD8+ T cells activated with immobilized anti-CD3 plus interleukin 2 showed marginal cytotoxicity against tumour cells. However, addition of the prepared BSAb into the culture resulted in a marked augmentation of the cytotoxicity by the activated CD8+ T cells in a dose-dependent manner. The enhanced cytotoxicity of CD8+ T cells in the presence of BSAb was specific for c-erbB-2 positive tumour cells. Moreover, it was demonstrated that anti-CD3 × anti-c-erbB-2 BSAb was also effective for the specific targeting of various kinds of in vitro-activated antitumour effector cells such as lymphokine-activated killer cells, CD4+helper/killer cells, γδ T cells and activated tumour-infiltrating CD8+ T cells. These results indicated that BSAb consisted of anti-CD3 and anti-c-erbB-2 will become a useful tool for the adoptive tumour immunotherapy of human cancer expressing C-erbB-2 oncogene products. [ABSTRACT FROM AUTHOR]

Previous studies established that the high density (resting) natural killer (NK) cell subset (R-NK) of peripheral blood NK cells is unresponsive to interleukin-2 (IL-2) but can be induced to proliferate when cultured with γ-irradiated malignant melanoma (MM-170) cells or rnitomycin-C-treated activated T cells in the presence of an IL-2-conditioned medium (IL-2-CM). This study has examined additional requirements of this activation process. The induction of proliferation was dependent on cell to cell contact with metabolically active stimulator cells, although no evidence was obtained that stimulation was effected by soluble factors produced by the stimulator cells. Compared with IL-2-CM, rIL-2 was an inefficient costimulator for the induction of NK cell proliferation, suggesting that factors in IL-2-CM were required in addition to IL-2, but rIL-2 was as efficient as IL-2-CM in maintaining the proliferation of activated NK cells. Under optimum culture conditions, NK growth of up to 3200-fold occurred during a proliferation cycle of 18 days. Phenotypic analysis of the culture-generated quiescent NK cells revealed novel heterogeneity in CD16 (FcγRIII) and CD56 (N-CAM) expression. Some NK cells lacked expression of both CD16 and CD56 (as identified using currently available monoclonal antibodies), while other NK cells showed differential CD16 epitope expression. Since quiescent NK cells can be obtained in large numbers and high purity, they will be a convenient source of NK cells to study the molecular processes involved in initiating NK cell proliferation. [ABSTRACT FROM AUTHOR]

The difficulty of transfecting primary macrophages and macrophage cell lines has meant that relatively few studies on regulation of gene expression have been performed in these cells. This study has optimized an electroporation procedure for the macrophage cell line RAW 264, but shows that introduction of DNA into the cytoplasm of primary macrophages by electroporation is toxic to the cells. It is proposed that this cell death may have a physiological role in defence against certain viral infections which result in accumulation of cytoplasmic DNA. RAW 264 cells were efficiently transfected by electroporation, but electroporated bone marrow derived macrophages (BMM) showed large scale cell death over a period of 12 h. Electroporation without DNA was not toxic and DNase treatment of samples before transfection prevented cell death. The toxicity of DNA was concentration-dependent and sequence-independent. Synthetic, genomic and plasmid DNA all caused cell death. This sensitivity to DNA seems to he distinct from the antiviral state induced by double-stranded RNA and may be part of an uncharacterized viral defence system. [ABSTRACT FROM AUTHOR]

The phenotype of milk-derived and peripheral blood lymphocytes from normal and coeliac subjects was assessed for CD3, αβ-TcR (T cell receptor), γδ-TcR. CD4, CD8, HML-l (human mucosal lymphocyte) determinants, and activation was measured by interleukin-2 receptor (IL-2R) expression. Milk cells from normal and coeliac subjects were analysed by manual immunofluorescence and milk and blood cells from normal subjects were analysed by flow cytometry. Milk cells from two coeliac subjects were tested for proliferation to gluten antigen. The CD4:CD8 ratio of milk lymphocytes from both normal and coeliac subjects was similar (0.78-1. 1). but lower than that present in blood (1.5-2.1). The IL-2R expression of milk lymphocytes from both coeliac and normal subjects was increased by 3-6 times corn pared with peripheral blood cells. For example. IL-2R was present on 27.3% of milk CD3+ lymphocytes and on 8.0% of blood CD3+ lymphocytes from normal subjects. γöδ- and HML-1+ T cells were increased 4.2-fold and 12-fold respectively compared with blood lymphocytes. Milk cells from coeliac subjects showed specific proliferation to gluten but not to soya bean antigen. We conclude that milk cells have a 'mucosal' phenotype. with increased γyδ-TcR. CD8+ and HML-1+ T cells, and have an increased proportion of activated cells. Milk cells from coeliac subjects have no 'toxic' phenotype. but show functional reactivity by specific proliferation to gluten antigen. [ABSTRACT FROM AUTHOR]

This report details experimental results which show the presence of enzymic aminopeptidase- A-like activity on endothelia cells, concomitant with cell surface expression previously detected by both ELISA and indirect immunofluorescence. This activity, detected using selected chromogenic substrates in 'functional' assays, is shown to be due (at least in part) lo a molecule previously termed 'gp 150' and recognized by MoAb belonging to CD-13, since such antibodies can he shown to inhibit this activity. Activity, as detected on endothelial ceils, is similar to that observed on various haemopoietic cells. These assays not only provide a functional basis to cell surface gp 150 (CD-13) co-expression on haemopoietic and endothelial cells but have also been used to help define structural epitopes present on aminopeptidase-N/gp 150, previously analysed using radiolabelled antibodies in competitive binding assays. Appraisal of these new data suggests that the number of distinct antibody binding sites on this molecule is greater than that previously demonstrated. This study is therefore an important first step in investigating the potential involvement of this selective peptidase molecule in the control of haemopoietie cell growth and differentiation and in haemostatic mechanisms. [ABSTRACT FROM AUTHOR]

Murine suppressor factors (SF) in tumour-bearer serum (TBS) and tumour-bearer spleen cell culture supernatants (SCCS) were compared with regard to their molecular markers, cellular requirements and suppressive activities. Suppressor factors in SCCS bear the idiotype I-J, and markers recognized by B16G and anti-lipomodulin antibodies require Ly2+ I-J+ cells for their production and cells of the same phenotypes, for suppression to be manifested in leucocyte adherence inhibition (LAI) assays, are not immunoglobulin (Igh)-restricted and are active in both the afferent and efferent phases of the immune response. Suppressor factors from TBS resemble those from SCCS with regard to idiotype, I-J and lipomodulin-like markers, but in contrast, do not bind to B16G antibody, require Ly2+ but not I-J+ cells for suppression to be manifested in LAI assays, are Igh-restricted, and suppress delayed-type hypersensitivity (DTH) reactions only when injected in the afferent phase. These results show that the SF from the different sources in tumour-bearing mice are not identical; they may be different parts of a suppressor cascade, or they may belong to entirely separate suppressor cascades. [ABSTRACT FROM AUTHOR]

Previous reports have documented that mice bearing plasmacytomas (PC) are suppressed in their ability to mount a primary antibody response, whereas cellular immunity appears to be normal. Studies presented here provide evidence that T cell responsiveness is also depressed in BALB/c mice bearing the Lieberman plasmacytoma (Lpc-1). For instance, splenocytes from mice bearing large tumours were impaired in their in vitro ability to respond to the T cell mitogen, mount an appropriate alloreactive cytolytic T lymphocyte response, and produce interleukin-2 (IL-2). A population of suppressor cells was detected in the spleens 7 days after tumour implantation as evidenced by their ability to prevent normal splenocytes not only from responding to antigens in mixed lymphocyte culture, but also from producing IL-2. A similar inhibitory effect was observed with culture supernatants of these cells, indicating the existence of a soluble suppressive factor. Therefore, the present study demonstrates that cellular immune responses are impaired in mice bearing Lpc-1 tumours and that this effect may be due to the generation of suppressor cells and/or a suppressive factor. [ABSTRACT FROM AUTHOR]

The neurovirulent strain of vaccinia virus, VV-WR, or recombinants derived from VV-WR, cause highly productive infection of murine ovaries, but infection could be partially inhibited in vivo using an antiserum to asialo-GM1 (as-GM1). In vitro analysis by flow cytometry revealed that murine ovarian cells expressed a cell surface antigen identical to or cross-reactive with as-GM1. The capacity of VV-WR to infect murine ovaries appears to depend in part upon as-GM1 expression on ovarian cells. [ABSTRACT FROM AUTHOR]

A technique is described for the culture of disaggregated rabbit keratinocytes and the production of confluent sheets of immunologically pure kerhtinocytes suitable for use in transplantation studies. The benefits of various feeder layers, nutrients and growth hormones were examined by the use of paired controls. The ability of the cultured keratinocyte sheets to be removed from the culture vessel intact and survive as viable autografts was demonstrated, thus establishing a new animal model for the investigation of allograft rejection responses to cultured keratinocytes. The benefits of using the rabbit model for such studies and the advantages of this culture technique over a previously described method of rabbit keratinocyte cell culture are discussed. [ABSTRACT FROM AUTHOR]

Detachment of epithelial structures from underlying basement membrane (BM) represents an important component of a number of human disease processes e.g. airway and alveolar diseases, gastrointestinal ulceration, and retinal diseases. This study describes a method of evaluating human epithelial cell detachment from BM that is simple, rapid, inexpensive, quantifiable and which, because it utilizes BM rather than tissue culture plastic, more closely mimics the in vivo situation than other methods. In this model human amnionic epithelial cells attached to their underlying BM are isolated from fresh placentae and mounted in a multi-well chemotaxis assembly. These membranes can be studied with the epithelial cell monolayer intact. Protease-induced detachment of the epithelial cells from the underlying BM was readily quantifiable using light microscopy and spectroscopy. Following removal of the native amnionic epithelial cells, immunoperoxidase staining for the BM attachment proteins laminin, fibronectin, and type IV collagen demonstrated that these molecules remain intact.The BM could also be used as an attachment surface to reconstitute other epithelial cell monolayers.Cultured human amnionic cells and human respiratory epithelial cells were both able to attach to the denuded BM in the absence of serum (% attachment = 85 ± 15% and 92 ± 8% respectively, P = 0· 8).Natural BM was a better substrate for epithelial cell attachment than tissue culture plastic in that, in the absence of serum, cultured epithelial ceil attachment to tissue culture plastic was 20 7plusmn; 4% of the value for BM (P < 0· 05). Furthermore, cells attached to plastic adhered less effectively than to BM in that trypsin concentrations required to induce 50% cell detachment were 0·72 ± 0·4 for plastic and 62± 13 BAEE U/mL for BM (P<07middot;001).In view of the complex protein interactions known to be involved in the anchorage of human epithelial cells to BM, it is likely this model will be a useful tool for evaluating the mechanisms underlying human epithelial cell attachment and detachment in a variety of normal and disease situations. [ABSTRACT FROM AUTHOR]

The distribution of interstitial collagenase in a rat mammary carcinoma model system has been studied by immunocytochemistry. Rabbit antibodies were raised against collagenase from neoplastic epithelial cells which were derived from an anaplastic, invasive, rat mammary carcinoma (BCl). Specificity of the antibodies was determined by Western blot analysis which showed reactivity with the inactive procollagenase from conditioned culture medium of BCl cells as well as with purified, active BCl collagenase. Anti-BCl collagenase antibodies did not recognize BCl collagenase entrapped by the inhibitor, rat α-2-macroglobulin (α2M). or collagenase derived from TPA-stimulated human fibroblasts. Anti-human fibroblast collagenase antibodies did not recognize BCl collagenase, suggesting that the human-mesenchymal and rat-epithelial enzymes are immunologically distinct molecules. Collagenase was immunolocalized intracellularly in BC1 cells cultured in the presence of monensin. Neither BCl collagenase, α2M nor enzyme-inhibitor complexes were demonstrated in or around invading tumors by immunostaining of tissue sections of rat mammary carcinomas. [ABSTRACT FROM AUTHOR]

Pertussis toxin (PT), a protein toxin of Bordetella pertussis, also called pertussigen, has a wide range of biological activities, including the induction of lymphocytosis. This phenomenon was investigated by studying lymphocyte circulation in mice. Lymph node cell suspensions were exposed to PT in vitro and then injected intravenously. A double radiolabel technique was employed, in which PT-treated and control cells were injected into the same animals. The protocol used in these experiments was chosen to demonstrate a direct effect of PT on the injected cells. After exposure to PT in vitro, cells were profoundly excluded from lymph nodes over the succeeding six days. Entry into both mesenteric and peripheral lymph nodes, but not into the spleen was inhibited by PT, and there was an accumulation of the PT-treated cells in the blood. Cells were excluded from the lymph nodes after treatment with as little as 2 ng/mL of PT. This dose was over two orders of magnitude lower than the threshold dose of the same PT preparation required to induce lymphocyte mitogenesis in vitro. The findings in the present communication are consistent with studies using genetically modified PT in which the ADP-ribosylating capacity of the A-subunit was necessary for the effect of PT on lymphocytosis. [ABSTRACT FROM AUTHOR]

This study investigated in vitro biological response modifiers (BRM) possibly involved in initiation and regulation of human capillary endothelial cell (HCEC) growth. An indicator assay was developed using tritiated thymidine to measure increased DNA turnover. Purified or recombinant BRMs tested singly and in combination included: interferon (IFN; α and γ), tumour necrosis factor (TNF; α and β), transforming growth factor (TGF; α and β), rIL-1, rIL-2, pIL-2, platelet derived growth factor (PDGF) and retinoic acid. Under limiting serum conditions only rIL-2 (≥10 U/mL) caused proliferation of the cells. γIFN together with TNFα(500 U/mL of each) was cytotoxic. Under maximal stimulus conditions, a cytostatic effect resulted from exposing HCEC to: α or γ IFN (≥ 1000 U/mL), TGFβ (≥5 ng/mL), rIL-1 (≥0.5 U/mL) and rIL-1 plus γ IFN. γIFN (500 U/mL) plus TNFα exhibited synergism in the inhibition of proliferation and produced a cytotoxic effect at TNFα concentrations ≥ 500 U/mL. By contrast, rIL-2 enhanced proliferation at >5 U/mL. When rIL-2 was combined with γIFN, an inhibitory effect on proliferation was observed, although to a lesser extent than γIFN alone. Pretreating the cells with 100 U/mL γIFN prior to rIL-1 or IL-2 exposure produced no change in the trends observed above. TGFα also stimulated cell proliferation at concentrations ≥0.5 ng/mL. PDGF and retinoic acid had no effect on proliferation in the concentration range 0.5–10 U/mL. By investigating the response of HCEC to these BRMs, the nature of, and response to the signals from immune cells in inflammatory disease processes can be better understood. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about the cell expression of thymocytes in the 2008 issue.

Burnet appreciated the requirement for self/non-self discrimination and presciently postulated elimination of auto-aggressive cells during early life. He could not have known that, for T cells, a limited degree of autoreactivity is beneficial for the immune system. Here, we review evidence that recognition of self-components keeps T cells alive and regulates self-tolerance.Immunology and Cell Biology (2008) 86, 54–56; doi:10.1038/sj.icb.7100139; published online 11 December 2007 [ABSTRACT FROM AUTHOR]

A hypothesis is proposed asking why enzyme neutralization is not an effective host-response to a parasite despite the fact that some parasite housekeeping enzymes are highly immunogenic. It is hypothesized that although the structural domain can be immunogenic, the active sites of the parasite enzyme molecules have converged evolutionarily to resemble the functional part (active sites) of host's enzyme molecules, by structural modification/rearrangement (amino acid substitution/polypeptide chain folding) with the effect: (i) of functional adaptation to the host environment; and (ii) to escape detection of active sites by the host as non-self, allowing the parasite to be exposed to antiparasite enzyme antibodies, without deleterious effects on the parasite. [ABSTRACT FROM AUTHOR]

The article focuses on the CD4 effector T-cell subpopulation, Th17T cells. It also states that these cells are said to be important in the pathogenesis of autoimmune diseases. According to a study, Th17 differentiation is individualized by a transcription aspect that is influential in lymphoid organogenesis. Ivanov and his colleagues, in another study, classified the nuclear retinoic acid-related orphan receptor RORγt as the transcription factor specifying the Th17 lineage.