bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Class I H‐2Db molecules primarily expressed by B lymphocytes in murine spleen
Authors: O'NEILL HELEN C.
Published: July 2007

Evidence is presented which supports the phenomenon of heterogeneity amongst H‐2Db‐encoded Class I molecules. Two monoclonal antibodies (MoAb) called H 141–31 and B22–249 were used in these studies. Both bind to the ‘private’ H‐2.2 site of H‐2Db‐encodcd molecules, but the binding of B22–249 is determined by carbohydrate moieties, whereas H 141–31 appears to bind to a protein‐defined epitope. Some H‐2Db molecules, identified by the H141–31 MoAb, are primarily expressed on B lymphocytes and not T lymphocytes in spleen. The number of H‐2Db molecules which bind H141–31 on B cells was also found to be three‐to four‐fold less than the number which bound the B22–249 MOAb, B cells of two mutant strains of mice, B6‐C.H‐2bm13 and B6‐C.H‐2bm14 which harbour very few nucleotide changes in the H‐2Db gene, also show marked reduction in the binding of both antibodies. This suggests that a single common gene encodes both target molecules and that post‐translational modifications such as differential glycosylation may account for heterogeneity amongst H‐2Db molecules. This would explain the presence of the different H‐2Db molecules defined here. It follows that differences in glycosylation evidently occur both within the B cell population, since H141–31 binds to only a subset of H‐2Db molecules on B cells, and between T and B lymphocytes, since resting T cells do not bind H141–31 MoAb.
Murine candidiasis: Sex differences in the severity of tissue lesions are not associated with levels of serum C3 and C5
Authors: ASHMAN R. B. , KAY P. H. , LYNCH D. M. , PAPADIMITRIOU J. M.
Published: July 2007

Mice deficient in the fifth component of complement are known to be extremely susceptible to lethal challenge with Candida albicans. However, male mice, that have significantly higher concentrations of serum C5 than females, were markedly more susceptible to infection. This difference was observed in both susceptible (CBA/H) and resistant (BALB/c) mice. Levels of serum C3 likewise showed no correlation with susceptibility.
Temporal variations in the fine specificity of IgM anti‐fluorescyl antibodies
Authors: DALESANDRO MARGARET R. , SKEATH JAMES B. , DORER DOUGLAS R. , SNYDER MARGARET M. , OWEN JUDITH A.
Published: July 2007

This study compares the fine specificities of the primary and secondary fluorescein (FITC)‐specific immunoglobulin M (IgM) repertoires in BALB/c mouse serum and monoclonal antibodies (MoAb) and has found reproducible, immunization‐dependent differences. FITC and four of its homologues: iodoacetamido fluorescein (IAF), dichlorotriazinyl aminofluorescein (DTAF), substituted rhodamine isothiocyanate (XRITC) and tetramethyl rhodamine isothiocyanate (TRITC), each conjugated to bovine serum albumin (BSA), were used to determine reactivity patterns of serum IgM from mice immunized once or twice with FITC‐haemocyanin (FITC‐Hy), Reactivity patterns were also obtained for 20 IgM MoAb, eight of which were produced by fusions of SP2/0 myeloma cells with splenocytes from mice immunized once (primary) and 12 from mice immunized twice (secondary) with FITC‐Hy. Each MoAb exhibited a unique line specificity pattern, evidence of extensive heterogeneity in the FITC‐specific repertoire. Reactivities of IgM MoAb with certain homologues were found to be more characteristic of either the primary or secondary response. Polyclonal serum IgM also showed reproducible immunization‐dependent variations in fine specificity. Such a pattern could result from idiotypic suppression of primary antibodies, from the expansion of subsets of IgM memory cells utilizing novel genes and/or from somatic mutation absent in primary IgM antibodies.
Effects of Freund's adjuvants on local, draining and lymphocyte populations in sheep
Authors: McCLURE S. J. , WAGLAND B. M. , EMERY D. L.
Published: July 2007

Lymphatic cannulation and serial biopsy were used to examine changes in cell lymphocyte populations after injection of adjuvant in order to explain the mechanisms of the subversive effect that Freund's adjuvants (FA) have on protective immunity against nematode parasites in sheep. Within 4 days of intradermal injection of complete or incomplete FA into sheep there was a selective depletion of the T19+ TCYγδ+ T lymphocyte subpopulation from efferent lymph draining the local lymph node. Transient depletion of CD8+, T19+ and CD5+ cells from jugular blood was evident at day 2. The adjuvant‐induced granuloma was a connective tissue/macrophage/T lymphocyte phenomenon, with no B cell follicles, and the T cell content continued to increase for the 21 days. The early granuloma (days 2–4) contained a disproportionate number of T19+γδ+ lymphocytes. It appeared that the adjuvants induced selective sequestration of this T cell subset during the initial period of granuloma formation.
Cloning and sequencing of the cDNA for ovine granulocyte‐macrophage colony‐stimulating factor (GM‐CSF)
Authors: O'BRIEN P. M. , ROTHEL J. S. , SEOW H‐F. , WOOD P. R.
Published: July 2007

Colony‐stimulating factors (CSFs) are not only regulators of haemopoiesis but can also enhance the function of mature myeloid cells, and are therefore potential immune adjuvants. By use of the polymerase chain reaction (PCR) with primers based on the bovine granulocyte‐macrophage CSF (GM‐CSF) sequence, we have amplified the cDNA for ovine GM‐CSF, produced from crude mRNA extracted from alveolar macrophages. The PCR product was cloned into pUC 119, and electroporated into Escherichia coli. The complete nucleotide sequence of two clones, and the partial sequence of eight others, was determined. At the nucleotide and amino acid levels, the ovine and bovine GM‐CSF sequences are 91% and 81% homologous, respectively.
Quantitative analysis of lymphokine expression in vivo and in vitro
Authors: TROUTT ANTHONY B. , MARASKOVSKY EUGENE , ROGERS LESLEY A. , PECH MICHAEL H. , KELSO ANNE
Published: July 2007

Constitutive lymphokine production by cells isolated from mice injected with keyhole limpet haemocyanin (KLH) or from mice undergoing an acute graft vs host reaction (GVHR) was very low, but could be markedly increased by T cell receptor (TCR) ligation. This suggested that in vivo levels of lymphokine production are much lower than those induced by in vitro stimulation. Serum lymphokine titres were consistent with this possibility, and analysis of lymphokine mRNA levels using S1‐nuclease protection demonstrated that in vitro‐stimulated cells from normal, KLH and GVHR mice all had markedly increased levels of lymphokine transcripts relative to levels found in vivo. A novel method combining limiting dilution analysis with polymerase chain reaction amplification of cDNA was developed that showed that these differences in levels of lymphokine production were due at least in part to differences in the frequencies of lymphokine mRNA‐containing cells. Studies of the means by which differential lymphokine production is achieved demonstrated that CD4+, CD8+ and cytotoxic T lymphocyte (CTL) clones all express a common, restricted set of lymphokines in response to a defined in vitro stimulus, but that individual in vivo primed cells can express at least seven distinct patterns of lymphokine production.
Technetium‐99 m labelling of DD‐3B6/22 antifibrin monoclonal antibody fragment Fab′ for thrombus imaging
Authors: LEE F‐T. , BONIFACE G. R. , LAMBRECHT R. M. , RYLATT D. B. , BUNDESEN P. G.
Published: July 2007

The antifibrin DD‐3B6/22 monoclonal antibody Fab′ fragment, a murine immunoglobulin, IgG3, has been labelled with technetium‐99 m (99mTc) via a transchelation reaction, to specific activity in excess of 30 mCi/mg protein. The radio labelling of Fab′ was dependent on time, temperature, pH, antibody concentrations and nature of intermediary transchelation complex used. The resultant radio conjugate was stable in vitro and in vivo. Blood clearance of 99mTc‐Fab′ in rat followed two compartment kinetics with the half time of the fast phase being 0.5 h. The main route of excretion was via the kidneys with little uptake indicated by other tissues. The results suggest that the inherent specificity of the antibody, small molecular size, rapid plasma clearance, high specific radioactivity, together with the physical properties of the 99mTc label, combine to make this labeled monoclonal antibody (MoAb), potentially suitable as a radiopharmaceutical for the scintigraphic detection of thrombi in humans.
In vivo inhibition of the rat primary antibody response to antigenic stimulation by somatostatin
Authors: EGLEZOS ANTHONY , ANDREWS PAUL V. , HELME ROBERT D.
Published: July 2007

Somatostatin inhibits in vitro lymphocyte proliferative responses from a variety of species including human, mouse and rat. The immunoinhibitory effects of somatostatin are thought to involve binding to specific cell surface somatostatin receptors on immunocompetent cells. This report describes an in vivo immuno inhibitory effect of somatostatin on the rat pophteal lymph node lymphocyte primary antibody response to sheep red blood cell (SRBC) stimulation. Infusion of somatostatin immediately following SRBC injection into the hind feet of rats had a dose‐related inhibitory effect. At the highest concentration used, 10 μmol/L, the level of inhibition was similar to that previously described following neonatal capsaicin treatment of rats. This suggests that neonatal capsaicin treatment may lead to decreased primary antibody responses to SRBC by a selective effect on tachykinin containing nerves and a lesser effect on somatostatin containing nerves. The immuno inhibitory effect of somatostatin was reversed by co infusion of neurokinin A but not substance P, both of which have been shown to stimulate this response. This suggests the possibility that multiple tachykinin receptors are involved in the modulation of the SRBC primary antibody response in vivo These results present evidence for an in vivo immunomodulatory role of somatostatin.
Immunochemotherapy of human colon carcinoma xenografts in nude mice using combinations of idarubicin‐monoclonal antibody conjugates
Authors: SMYTH MARK J. , FOSTER HAMISH McA. , ANDREW SARAH. M. , KRAUER KENIA , McKENZIE IAN F.C. , PIETERSZ GEOFFREY A.
Published: July 2007

Tumour cell heterogeneity is probably a principal cause of treatment failure and represents a formidable barrier for effective antibody‐targeted chemotherapy. Idarubicin (Ida), a more potent and less cardiotoxic analogue of daunomycin, has been demonstrated to specifically target and eradicate homogeneous, cloned, murine tumour cell populations in vitro and in vivo when coupled to monoclonal antibodies (MoAb); however, the antitumour activity of Ida‐MoAb conjugates against human tumour xenografts remains to be established. In this study, the value of cotargeting conjugates to different human tumour‐associated antigens within a solid tumour has been assessed by comparing the effects of combinations of Ida‐anti‐colon carcinoma MoAb conjugates with any one Ida‐anti‐colon carcinoma MoAb conjugate used alone. Individual Ida‐MoAb conjugates have previously been evaluated for their specific binding and cytotoxicity to one of two different human colon carcinoma xenografts (Colo 205 or LIM2210) in vitro, although their efficacy alone or in combination required assessment in vivo. Combinations of the most effective Ida‐MoAb conjugates were demonstrated to enable a greater number of complete tumour regressions than the most efficacious Ida‐MoAb conjugate administered alone in vivo; some combinations inhibited control tumour growth by up to 95%. This study suggests that Ida‐MoAb conjugates can be effective against subcutaneous human tumours in nude mice, although it is unlikely that any single conjugate will eradicate all the tumour cells in a solid tumour, and the value of ‘cocktails’ of drug‐MoAb conjugates against some xenografts (i.e. LIM2210) appears to be limited.
Interleukin‐6 production during chronic experimental infection
Authors: SAUNDERS BERNADETTE M. , LIU ZHANQI , ZHAN YIFAN , CHEERS CHRISTINA
Published: July 2007

The appearance of interleukin‐6 (IL‐6) in serum of mice was monitored during the course of chronic infection with either Brucella abortus vaccine strain 19 or a virulent Mycobacterium avium Complex (MAC) isolate. Serum IL‐6 during brucella infection was higher than during infection with MAC, despite similar numbers of bacteria. Furthermore, IL‐6 titres decreased after the peak of infection, falling to baseline levels before these chronic infections were eradicated. The ability of peritoneal cells or spleen cell suspensions to produce IL‐6 under either specific or non‐specific stimulus was greatly enhanced by infection. While production of IL‐6 by these cultures was apparently mostly independent of T cells, T cells from infected mice could produce an lL‐6 response. Thus CD4+ T lymphocytes prepared from mice which had recovered from B. abortus infection, cultured with antigen and antigen presenting cells, resulted in IL‐6 production, which was not observed in similarly cultured CD8+ T cells, indicating a role for T cells.
Production of transferrin by human cell lines in a defined protein‐free system: Detection by ELISA
Authors: KRIEGERBECKOVÁ K. , KOVÁŘ J. , NEUMANNOVÁ V.
Published: July 2007

A double sandwich enzyme immunoassay using a combination of two polyclonal and one monoclonal antibodies was developed to quantitate transferrin in various human cell lines (U 937, K 562, Jiyoye, Jurkat, Raji, THP‐1, HeLa) and transferrin secreted by these cells cultured in a defined protein‐free medium. In the developed assay the measurable range in our experimental system is 1 to 25 ng/mL of human transferrin and the interassay coefficient of variation ranged from 11.3 to 16.1%. The assay is specific for both transferrin and apotransferrin with the same sensitivity. Intracellular transferrin levels in all the cell lines tested were < 1 ng/106 cells. The highest level of transferrin was found in cells of the histiocytic line U 937 (0.84± 0.18 ng/106 cells). Only this cell line secreted transferrin in amounts > 1 ng/106 cells per day, i.e. 15.8 ± 2.3 ng/106 cells per day. Intracellular transferrin was also demonstrated by immunoblotting.
Tumour‐Specific CTL response requiring interactions of four different cell types and recognition of MHC class I and class II restricted tumour antigens
Authors: SCHIRRMACHER VOLKER , SCHILD HANS‐JÖRG , GÜCKEL BRIGITTE , VON HOEGEN PAUL
Published: July 2007

This study demonstrates that a syngeneic specific cytotoxic T lymphocyte (CTL) response to a class I major histocompatibility complex (MHC) positive tumour requires dual processing and recognition of tumour antigens. One type of antigen is processed and expressed in association with class I MHC at the surface of intact tumour cells. It is recognized by CD8 α,β TCR CTL in vitro and by protective immune T cells in vivo and thus functions as a tumour‐associated transplantation antigen (TATA). The other type of antigen is processed and expressed by distinct host APC in association with class II MHC. This is recognized by immune CD4 T cells which function as essential helper cells in the generation of the CD8 CTL response. These conclusions are supported by cell depletion and reconstitution experiments as well as by blocking experiments with monoclonal antibodies using the highly metastatic class II negative murine lymphoma ESb as a model system. The existence of two types of cognate T cell responses in a syngeneic anti‐tumour response was directly proved by the establishment of two types of tumour specific T cell lines which required as co‐stimulator either MHC class II positive APC or IL‐2. In suboptimal mixed lymphocyte tumour cell cultures either of these co‐stimulator functions was found to be limiting the overall anti‐tumour CTL response. The generation of the tumour specific CTL response could be blocked by monoclonal antibodies against all the molecules involved in the cognate interactions (i.e. class I MHC, CD8, class II MHC, CD4 and TCR) but not by anti‐CD2 or anti‐IgG. The strict requirement for helper cells and APC could be bypassed by the addition of recombinant IL‐2 but optimal triggering of CD8 CTL‐precursor required viable tumour stimulator cells. This well characterized in vitro assay may be useful (i) for monitoring the immune status of CD4 and CD8 immune T cells separately, for instance of tumour bearing and/or treated animals and (ii) for the development and testing of potent tumour cell vaccines with T cell stimulatory and/or co‐stimulatory activities.
Images of self: A model for tonic peripheral tolerance
Authors: RUDY G. , LEW A. M.
Published: July 2007

A model for peripheral tolerance is proposed in which immune reactivity is controlled by the presence (cf. absence) of CD4+ T cells. Continuous ‘tonic’ recognition of self is maintained throughout adult life by, among others, a subset of ‘autoreactive’ CD4+ T cells recognizing ‘dominant’ determinants derived from self‐antigens. It is hypothesized that these cells have survived intrathymic deletion to be tolerized in the periphery, where they continue to function by tolerizing other similarly reactive thymic emigrants. This ‘image’ of self is postulated to arise during fetal and early neonatal life, remaining largely invariant thereafter, and serves as the backdrop against which recognition of ‘non‐self’ occurs. The model is discussed in the context of two examples of experimental autoimmune disease: induced autoimmunity in the 2–4 day old neonatally thymectomized mouse and spontaneous diabetes in the non‐obese diabetic (NOD) mouse.
High and low responsiveness to vaccines in farm Animals
Authors: OUTTERIDGE P. M.
Published: July 2007

Low responsiveness in some farm Animals is emerging as a problem in the application of newly developed vaccines which operate at skin surfaces and mucous membranes. Breeding for resistance to specific diseases seems to be associated with breeding for specific immune responsiveness in farm Animals and very likely this involves selection for major histocompatibility complex (MHC) haplotype. However, other factors contribute to low responsiveness and these include poor nutrition, sire effects, antigenic competition and inadequate effector mechanisms. The future of newly developed vaccines will rest on the solution to the low responder problem, and once solved, the application of these vaccines will be fully utilized for disease control in farm Animals.
Theoretical Article Adhesive interactions in thymic development: Does selective expression of CD45 isoforms promote stage‐specific microclustering in the assembly of functional adhesive complexes on differentiating T lineage lymphocytes?
Authors: PILARSKI LINDA M.
Published: July 2007

CD45 isoform transitions appear to play essential roles in both life and death, and correlate with the stages of thymocyte development during which there is a change in physical location from medullary and/or outer cortical areas to the inner cortex. This work speculates that CD45 isoforms, through a focal role in the assembly of adhesive complexes mediated by the external domains, participate in the maintenance and/or modulation of migratory behaviour by differentiating thymocytes, or alternatively in the anchoring of thymocytes in a generative micro‐environment. The objective of the sections that follow is to formulate the hypothesis that CD45 isoforms, through their differential interactions with adhesion molecules expressed by T cells, profoundly influence cell motility and consequent micro‐environmental localization. An adhesive assembly of CD45 and adhesion molecules on the outside, and of the adhesive complex with the cytoskeleton on the inside, would promote CD45‐mediated regulation of adhesion/de‐adhesion through lateral external interactions mediated by external domains of CD45 isoforms, through enzymatic modulation of the cytoplasmic domains of adhesion molecules by the CD45 tyrosine phosphatase activity, and through phosphatase control of cytoskeletal assembly and disassembly.
T cell receptor polymorphisms in Caucasians and Polynesians
Authors: ABBOTT W. G. H. , TAN P. L. J. , SKINNER M. A. , MARBROOK J. , PEAKE J. S. , WOODFIELD D. G. , GEURSEN A.
Published: July 2007

The purpose of this study was to find genetic polymorphisms that might be useful in studies of Polynesian‐Caucasian racial admixture and Polynesian disease susceptibility. The allele frequencies of six T cell receptor locus RFLP were measured in 73 Caucasians and two Polynesian ethnic groups comprising 86 Maoris and 95 Samoans. The RFLP studied were (locus/enzyme/probe): Cα/Taq1/Y14, Vα/Taq1/Y14, Cβ/BglII/Y35, Cγ/PvuII/HGP02, Vβ7/Bam HI/Vβ7.4 and VP8/Bam HI/Vβ8.1. Racial differences in allele frequency were present with all six RFLP (P < 0.001). The allele frequencies of the Vα/Taq1/Y14 and the Vp7/Bam HI/7.4 RFLP were similar in the two Polynesian groups, both of which differed from the Caucasians. The 1.4 kb allele of the Vα/Taq1/Y14 RFLP and the 8.0 kb allele of the Vβ7/Bam HI/7.4 RFLP were present in low frequency in both Polynesian groups compared to the Caucasian group, consistent with a gene flow effect. These alleles may be useful in studies of Caucasian–Polynesian racial admixture.
Stimulation of gastrointestinal antibody to Shiga toxin by orogastric immunization in mice
Authors: SUCKOW MARK A. , KEREN DAVID F. , BROWN J. EDWARD , KEUSCH GERALD T.
Published: July 2007

Shiga toxin (ST) is a protein toxin of Shigella dysenteriae type 1, a causative agent of severe diarrhoea and dysentery. In this report we describe the gastrointestinal secretory antibody response of mice following orogastric immunization with ST. Gastrointestinal secretions were sampled by a gastrointestinal lavage technique weekly for 5 weeks after initial immunization. Assay of lavage samples by ELISA showed that mice vaccinated orogastrically with various doses of ST developed gastrointestinal antibody to ST in a dose‐dependent manner. Serum anti‐ST activity developed by 5 weeks after initial immunization. The ability of ST to act as a mucosal immune adjuvant was investigated by coadministration of ST and keyhole limpet haemocyanin. In contrast to cholera toxin, a potent adjuvant, ST did not demonstrate adjuvant activity. The mouse gastrointestinal lavage model could be useful for further analysis of the cellular basis of ST immunogenicity.
The enigma of cytokine redundancy
Authors: KELSO ANNE
Published: July 2007

The redundancy of many cytokine functions that was first noted in vitro has now been confirmed in vivo with the demonstration that some of these functions can occur in mice rendered deficient in a cytokine or cytokine receptor by gene inactivation. Other functions are ablated in these mice, suggesting that they are cytokine‐specific. Although some of the underlying mechanisms have been identified, it remains unclear why certain activities of a cytokine should be unique and others redundant. It is proposed that compensatory mechanisms exist only for those cytokine functions whose inappropriate or excessive activation would not be pathogenic or whose importance justifies this risk. Conversely, cytokine‐specific functions might be those that should be tightly regulated to avoid the pathological consequences of their inadvertent expression.
Genetic polymorphisms of the non‐obese diabetic (NOD) mouse
Authors: McCLIVE PETER J. , BAXTER ALANG. , MORAHAN GRANT
Published: July 2007

The non‐obese diabetic (NOD) mouse is a polygenic model of insulin‐dependent diabetes. To better understand the biology, immunology and genetics of this mouse strain NOD mice were typed for RFLP at 29 loci and microsatellite variation at a further nine loci. Mice were also typed for the expression of lymphocyte differentiation antigens. Comparisons were made with two non‐diabetic strains, C57BL/6 and SJL, for these markers. A number of restriction fragment length polymorphisms (RFLP) were defined; seven between C57BL/6 and NOD; five between SJL and NOD; and four in which both C57BL/6 and SJL differed from NOD. Previously reported microsatellite results were extended by defining the SJL alleles at these loci, finding five loci at which NOD differed from B6 alone, and four loci at which NOD differed from both B6 and SJL. In addition, the NOD Igh allotype and alleles for a number of lymphocyte differentiation antigens were defined for the first time. The expression of uncommon alleles of these antigens suggests candidates whose role in the diabetogenic process can be tested.
Assays for adjuvanticity of new formulations and of carrier proteins for inducing antibody responses to selected immunogens in the squirrel monkey Saimiri sciureus
Authors: PERRAUT RONALD , CHOUTEAU PHILIPPE , BOURREAU ELIANE , BONNEMAINS BERNARD , GARRAUD OLIVIER
Published: July 2007

Different ways to improve antibody (Ab) responses following immunizations with selected antigens (TT and HSVgD) were investigated, and thus new adjuvant formulations and carrier molecules in a non‐human primate experimental host, the squirrel monkey Saimiri sciureus, were assayed. Both quantitative and qualitative humoral responses were determined by means of radio‐immunoassays using monoclonal Ab directed at Saimiri IgG. First, the adjuvanticity of the Syntex (SAF‐1) adjuvant and of five new adjuvant formulations were assessed towards the selected Ag. This indicated that all the adjuvants induced similar antigen‐specific Ab responses, although the adjuvants could modify to some extent the pattern of the qualitative Ab response. Second, we evaluated an adjuvant‐free vaccine approach using a synthetic Ag from the circumsporozoite protein of Plasmodium falciparum as immunogen, this Ag being coupled to purified protein derivative (PPD) or to a recombinant heat shock protein from Mycobacterium tuberculosis. These constructs led to good antibody responses as well as an excellent memory effect. Bacille Calmette‐Guerin (BCG) priming was required in conjunction with PPD as a carrier molecule to allow homogeneous Ab responses, whereas the heat shock protein construct gave a less homogeneous Ab response regardless of whether a BCG priming was done. We, in addition, discuss the relevance of Saimiri monkeys as experimental models for studies directed at evaluating the immunogenicity of further vaccine candidates.
Neuropeptide depletion by capsaicin does not prevent mucosal mast cell activation in the rat at weaning
Authors: CUMMINS A. G. , ANTONIOU D. , THOMPSON F. M.
Published: July 2007

Substance P release by enteric nerves could be an initiating factor for mucosal mast cell (MMC) activation that is associated with weaning in the rat. Capsaicin, which depletes substance P from enteric nerves, should therefore prevent MMC degranulation. Rat pups received either capsaicin (50mg/kg) or vehicle control subcutaneous injections at 3 and 6 days of life. Capsaicin‐treated and control litters were killed at 16, 18, 20, 22, 24 and 26 days of life. MMC activation was measured by serum levels of rat mast cell protease II (RMCPII). Intestinal development was assessed by microdissection to measure villus area, crypt length and crypt cell production rate. RMCPII levels were similar in capsaicin‐treated and control rats and peaked at day 22 of life, and intestinal development was not retarded by capsaicin treatment. We conclude that substance P release is unlikely to be an initiating factor for the MMC activation that is associated with weaning.
Role of insulin‐like growth factor‐1 on the kinetics of human lymphocytes stimulation in serum‐free culture medium
Authors: SCHILLACI ROXANA , RIBAUDO CLAUDIA M. , RONDINONE CRISTINA M. , ROLDÁN ALICIA
Published: July 2007

In a serum‐free medium addition of insulin‐like growth factor‐1 (IGF‐1) consistently enhanced lymphocyte proliferation response to PHA in a dose‐dependent fashion. This effect was produced by an acceleration in the expression of clone expansion and not in the number of proliferating cells. This was documented by kinetics data obtained from the first proliferation round of PHA‐stimulated lymphocytes, in which addition of IGE‐1 reduced G1‐phase length, without changing Go‐phase, S‐phase or cloned size. The data were confirmed in 10‐day culture of stimulated lymphocytes where IGF‐1 only accelerated cell proliferation without modifying the area enclosed by the proliferation curve. As IGF‐1 is under the control of growth hormone, our results suggest that some of the immunoregulation effects ascribed to growth hormone in vivo could be produced by IGF‐1.
An association between successful vaccination against the bovine nodular worm, Oesophagostomum radiatum and induction of eosinophilia
Authors: EAST IAIN J.
Published: July 2007

Immunization of 48 cattle with somatic antigen extracts of the nodular worm, Oesophagostomum radiatum, reduced faecal egg counts (FEC) by 51% and worm burden by 47%. The antibody titre of each animal was correlated to both worm burden (< r=−0.40, P < 0.005) and FEC (r=−0.37, P < 0.01). The vaccinated cattle showed wide variation in their response to vaccination with worm burdens after challenge infection varying from 0 to 4060. Of these 48 vaccinated animals, eight developed sterile immunity (worm burden = 0, FEC = 0) whereas a further 10 had no protective response to immunization (worm burden > 1000, FEC > 100). A comparison of these two sub‐groups showed that the group with sterile immunity had a higher antibody titre (P < 0.05). In addition, the group with sterile immunity developed a blood eosinophilia between 21 and 29 days after challenge infection. Vaccinated, unprotected calves and control, unvaccinated calves did not develop eosinophilia.
Attenuation of adjuvant arthritis in rats by treatment with oxygen radical scavengers
Authors: SANTOS L. , TIPPING P. G.
Published: July 2007

The contribution of reactive oxygen species (ROS), in particular hydroxyl radical (OH ·), to joint inflammation was examined in rats developing adjuvant arthritis (AA) by treatment with ROS scavengers dimethylthiourea (DMTU) and DMSO. Adjuvant arthritis was induced in Sprague‐Dawley (SD) rats by a single intradermal (i.d.) injection of Mycobacterium tuberculosis (MT) in oil on day 0. By day 14, all rats exhibited arthritis in the hindlimbs and the majority had involvement of the forelimbs. A marked inflammatory cell influx (75% neutrophils) was present in the synovial fluid. These cells, in vitro, spontaneously produced OH. (0.96±0.28 OH. units/h per 105 cells). In contrast, spontaneous OH· production by normal circulating leucocytes was absent (0.07±0.03 OH· units/h per 105 cells). Adjuvant‐injected rats were treated with DMTU (500, 250 and 100 mg/kg). DMSO (330 and 165 mg/kg) or saline (disease control) once daily on days 8, 9 and 10 and twice daily on days 11, 12 and 13 postadjuvant injection. Both DMTU and DMSO significantly reduced the clinical evidence of arthritis (clinical scores: DMTU [500 mg/kg] = 0. P < 0.0001: DMSO [3.0 mL/kg] = 0.4±0.3, P < 0.01, compared with disease control = 2.3±0.3). Synovial fluid cell accumulation was also significantly reduced (DMTU [500 mg/kg] = 0.5 ·0.1 × 105 cells/four joints, P < 0.0001; DMSO [3.0 mL/kg] 2.75 ± 1.9 × 105 cells/four joints, P < 0.01 compared with disease control = 11.76 ± 1.7 × 105 cells/four joints). Neither treatment inhibited cutaneous delayed type hypersensitivity (DTH) to the disease inducing antigen. Furthermore, DMTU (500 mg/kg) did not cause neutropenia nor inhibit peritoneal neutrophil accumulation in response to a chemotactic stimulus. This study demonstrates the attenuation of adjuvant arthritis by ROS scavengers and suggests a pivotal role for ROS, particularly OH·, in the mediation of joint inflammation in this disease.
Modulation and recovery of immune response of BALB/c mice to Shigella dysenteriae antigens after cyclophosphamide treatment
Authors: MISHRA KRISHNA K. , SRIVASTAVA AMIT K. , KAR SANTOSH K.
Published: July 2007

We have analysed the suppressive effect of cyclophosphamide. when given in vivo, on the antibody response of BALB/c mice against Shigella dysenteriae antigens using ELISA and immunoblot. Out of various protocols tried, it was found that co‐injection of cyclophosphamide at 150 mg/kg bodyweight, i.p., at the time of antigen administration and then after a lapse of 24 h during both primary and secondary immunizations, was the most effective in suppressing antibody response of mice. Analysis of sera by ELISA demonstrated the presence of some antibodies to S. dysenteriae antigens after secondary immunization, but immunoblot analysis using the same sera revealed complete suppression of antibody response. Animals whose antibody response was almost completely suppressed after two immunizations with co‐injection of cyclophosphamide, when immunized again after the lapse of 14 days from the date of secondary immunization with Shigella antigens but without administration of cyclophosphamide, partially recovered their ability to respond to the same antigens. This protocol can now be used in mice to analyse the hierarchy of immunogenic epitopes present in a complex mixture of antigens.
Comparison of cord blood and adult blood lymphocyte normal ranges: A possible explanation for decreased severity of graft versus host disease after cord blood transplantation
Authors: BECK R. , LAM‐PO‐TANG P. R. L.
Published: July 2007

Lymphocyte subpopulations in cord blood (CB; collected at birth from full‐term babies) were compared with that of adult blood (AB) and found to contain significantly different numbers and percentages of lymphocyte subpopulations. The absolute lymphocyte count was greater in CB (4.8 ± 1.1 × 109/L) than in AB (1.69 ± 0.38 × 109/L), with CB having significantly higher absolute numbers of lymphocyte subsets even though CB percentages were significantly lower. Significant differences in percentages were found between cord and adult T cells (CB 58% vs AB 74%), NK cells (CB 19% vs AB 7%) and their subsets. CD38, a marker of activation and immaturity, was present on virtually all cord T cells and approximately half the adult T cells. CD45RA, a marker considered to define unprimed or naive cells, was expressed on 82% of cord lymphocytes as compared with 48% in AB. CD45RO was expressed on 16% of CB lymphocytes and 49% of AB lymphocytes. Cord blood contains a higher percentage and total number of immature and immunologically naive lymphocytes than AB.
HLA‐A incompatibility associated with enhanced long‐term renal graft survival in HLA‐B, DR mismatched transplants
Authors: BUĆIN D. , EKBERG H. , LINDHOLM A. , PERSSON H. , TUFVESON G. , ALBRECHTSEN D.
Published: July 2007

The effect of HLA‐A matching on long‐term cadaver kidney graft survival was analysed, on average, 6 years after transplantation in a total of 1085 cyclosporine (CyA)‐treated patients.

A beneficial effect of HLA‐A mismatching on graft survival was found by univariate and multivariate analyses (P < 0.05).

Enhanced graft survival was associated with HLA‐A mismatching in transplants mismatched for HLA‐B,DR (P= 0.03), but not in HLA‐B,DR compatible transplants.

High 6 year graft survival rates, 78% and 66%, were found in transplants mismatched for two or one HLA‐A antigens, respectively, among patients without any acute rejection episode. This was significantly higher than the survival rate of 55% found in HLA‐A compatible transplants (P= 0.001). In patients who had suffered from acute rejection episodes, a prolonged graft survival was also associated with HLA‐A mismatching in HLA‐B,DR mismatched transplants (P= 0.04).

The beneficial effect on graft survival of HLA‐A mismatching was most pronounced in patients treated with high/medium dose CyA and prednisolone (P=0.004 overall and P= 0.0007 for HLA‐B,DR mismatched transplants).

In conclusion, HLA‐A mismatching was associated with enhanced long‐term renal graft survival in CyA‐treated recipients of HLA‐B,DR mismatched transplants. In clinical situations, the present results might, if confirmed, contribute to the prolongation of long‐term graft survival. The results might indicate the existence of tolerance promoting allogeneic markers within the HLA‐A class I region.
Regulation of C3 deposition on gp120 coated CD4 positive cells by decay accelerating factor and factor H
Authors: SADLON T. A. , PARKER S. J. , GORDON D. L.
Published: July 2007

We investigated complement activation by recombinant gp120 (rgp120) treated CD4 cells and the role host complement regulatory proteins play in controlling C3 deposition. Complement activation was determined by detection of C3 on rgp 120 coated cells in the presence and absence of HIV seropositive sera using flow cytometry. Treatment of rgp 120 coated cells with complement resulted in C3 deposition only if HIV positive sera was included. Examination of C3 fragments on these cells demonstrated rapid cleavage of C3b to iC3b. The role of the regulatory proteins was examined by pretreating cells with mAb to block decay accelerating factor (DAF) or membrane cofactor protein (MCP) or by using factor H depleted sera as a complement source. Inhibition of DAF or use of factor H depleted sera significantly increased C3 deposition on rgp120 coated cells. In contrast, C3 deposition on rgp120 coated cells was not increased after blocking MCP. The sensitivity of rgp120 coated cells to complement lysis was unchanged after inhibition of the regulatory proteins, despite the increase in C3 deposited. These results indicate that in a model of virus infected cells, C3 deposition is regulated by DAF and factor H but MCP appears to have no role.
Differential expression of CD45R0 on natural killer (NK) cells in patients with an NK lymphocytosis
Authors: WARREN HILARY S. , KINNEAR BEVERLEY F. , SKIPSEY LOUISE J. , PEMBREY RICHARD G.
Published: July 2007

NK cells from three donors with a NK (CD3− CD56+ CD 16+) lymphocytosis of unknown aetiology showed differential expression of CD45R0, an isoform of CD45 not expressed by NK cells from normal donors unless stimulated to proliferate in vitro. For donor FC, 60% of NK cells expressed CD45R0 over a 16 month period during which there was a partial resolution of the NK lymphocytosis. For donor SW, 37% of NK cells expressed CD45R0, increasing to 87% over a 14 month period during which the NK lymphocytosis increased. For donor RN few if any NK cells expressed CD45R0. After in vitro proliferation, 100% of NK cells generated from all donors expressed CD45R0. For donors FC and SW, CD45R0 remained expressed on more than 90% of cells at 3–4 weeks following cessation of proliferation. By contrast CD45R0 expression was gradually lost during long‐term culture of NK cells from donor RN, with 58% of NK cells regaining the pre‐culture CD45R0‐phenotype. NK cells from normal donors also varied in the extent to which activation acquired CD45R0 was lost during long‐term culture. The results obtained are consistent with the notion that NK cells from the NK lymphocytosis donors studied have previously undergone proliferation in vivo.
Politics, personalities and the development of science
Authors: LAFFERTY KEVIN J.
Published: July 2007

This lecture recounts a story that attempts to trace the history of ideas relating to tissue transplantation from the earliest times through to the present. This story was shaped by the strong Darwinian approach to biology championed by Burnet and Medawar. It also describes the political influence developed from the strong Lamarckian leanings of the communist supporters in the USSR, and the fact that the biological argument between those supporting Lamarck and those supporting Darwin was seen by the Praesidium of the USSR Academy of Sciences to be equated with the ideological class struggle between socialism and capitalism. This story points out that while science is valued for its objectivity, its dependence on personalities adds a subjective element. This subjective element is always present and it colours our science by reflecting both the political and cultural movements of the time.
Why do class I MHC molecules bind smaller peptides than class II MHC molecules?
Authors: BLANDEN R. V.
Published: July 2007

This article attempts to assemble theoretical‐teleological argument to explore possible answers to the question of why class I MHC molecules bind smaller peptides than class II MHC molecules and the associated question of why the size of peptides binding to class I molecules is approaching the limit of the self‐non‐self discrimination. I propose that the small size of most class I‐binding peptides precludes the production of ‘MHC‐restricted’ antibodies. Such a strategy avoids the possibility of antibodies binding to the epitopes recognized by CD8+ T cells, thus blocking effector function required for clearance of potentially lethal infections.
Do autoantibodies to IgE play a role in IgE‐mediated events?
Authors: SHAKIB FAROUK , SMITH SUSAN J. , PRITCHARD DAVID I.
Published: July 2007

Elevated blood levels of IgG anti‐IgE are detectable in individuals exhibiting enhanced IgE production, namely those with allergic conditions and helminthic parasite infections. The fact that there are epitope‐specific subpopulations of autoanti‐IgE suggests that this autoantibody could potentially have multiple effects in immunological events involving IgE.
Hypothesis: A memory lymphocyte‐specific soma‐to‐germline genetic feedback loop
Authors: ROTHENFLUH HARALD S.
Published: July 2007

Analysis of recently published DNA sequence data obtained for related germline Ig variable (IgV) genetic elements of several vertebrate species revealed the presence of a number of extremely non‐random patterns of sequence variability among these genes. Strikingly, the patterns were also observed in two sets of chicken IgV pseudogenes. Since the observed patterns are clearly incompatible with existing theories of multigene family evolution, a new model that can account for all of the data is presented in this paper. The model is a modification and extension of an earlier proposed mechanism whereby somatically expressed genes can be returned to the germline by endogenous retroviruses that may act as soma‐to‐germline genetic vectors. The mechanism described proposes that the interactions that may result in the soma‐to‐germline transfer of somatically selected IgV genes occur in the epididymis of the male reproductive tract and are restricted to memory lymphocytes. This mechanism makes a number of predictions that are amenable to experimental testing. From the data presently available in the literature it is not possible to extend the mechanism to the female reproductive tract.
Recombinant expression of vaccinia virus‐encoded TAP1 and TAP2 promotes MHC class I‐restricted antigen presentation in a Syrian hamster cell line
Authors: LOBIGS MARIO , MULLBACHER ARNO
Published: July 2007

Transporter associated with antigen presentation (TAP) molecules supply small peptides to the lumen of the endoplasmic reticulum for assembly with MHC class I glycoproteins. Here we report that a Syrian hamster cell line, BHK, which is commonly used in cell biological and virological investigations, is deficient in antigen presentation in a xenogeneic model. Thus when the mouse MHC class I restriction element, Kd, is expressed in BHK cells via a vaccinia virus (VV) recombinant, no significant recognition by VV‐immune and Kd‐restricted cytotoxic T cells is induced. This defect is apparently a consequence of a deficiency in TAP‐dependent peptide transport and can be repaired when rat TAP1 and TAP2 are provided by recombinant VV expression.
Effect of visible light on some cellular and immune parameters
Authors: KUBASOVA TAMARA , HORVÁTH MAGDOLNA , KOCSIS KATALIN , FENYÖ MÁRTA
Published: July 2007

The biological effect of visible light of low energy density was investigated in this study. The effects of diffuse (DL) and linearly polarized (LPL) light were compared on models in vitro and in vivo.

Experiments in vitro were performed on human lymphocytes to study their blast‐transformation and rosette‐formation abilities. Both DL and LPL increased the number of blast‐transformed cells even in a lymphocyte culture without PHA, and reduced rosette‐formation of T lymphocytes. LPL had a more pronounced effect.

In vivo exposure to DL and LPL of the spleens of tumour‐bearing mice caused the appearance of factor(s) in their serum, inhibiting the incorporation in vitro of [3H]‐thymidine into the tumour cells obtained from non‐exposed animals. In the other series of experiments serum samples were taken from tumorous animals after the exposure of their spleens to LPL. Following the daily administration of these sera to another group of non‐exposed tumorous mice a decreasing tendency of the mitotic kinetics of ascites tumour was observed.

The application of visible (preferably linearly polarized) light for the stimulation of human immune competent cells, and clinical trials with extracorporeal irradiation of blood for the promotion of natural defences of an immune‐repressed organism are suggested.
Effect of TGF‐β on differentiated organoids of the colon carcinoma cell line LIM 1863
Authors: HAYWARD IP , WHITEHEAD RH , WARD L , GIANELLO R , DEMPSEY P , BATES R , BURNS GF
Published: July 2007

The LIM 1863 colon carcinoma cell line grows in suspension as morphologically and functionally organized organoids in serum‐containing medium. Addition of TGF‐p caused the organoids to adhere and inhibited DNA synthesis. A 20 min incubation with TGF‐β was sufficient to induce adherence and this could be inhibited by cycloheximide. The adhesion and DNA synthesis inhibition were demonstrated to be separate events. We were not able to detect any changes in matrix or cell membrane antigens. Similarly there were no changes in synthesized proteins (by two‐dimensional gel electrophoresis), and no upregulation of proteoglycan. When adhered organoids were lysed from the tissue culture plastic surface, untreated organoids adhered to this surface. This ‘conditioned’ surface was destroyed by trypsin but not collagenase or medium from normal LIM 1863 cultures. However, the adherent phenotype was prevented when organoids were treated with transforming growth factor‐β (TGF‐β) in the presence of medium conditioned by normal LIM 1863 cultures rather than in fresh medium. The adhesion process was inhibited by an antibody (QE2E5) against β1 integrin although no quantitative changes in integrins were observed (by immunoprecipitation or RNA analysis). A second anti‐β1 integrin antibody (61.2C4) inhibited LIM 1863 adhesion to collagen but not TGF‐β induced adhesion, implying that TGF‐β induced a specific conformational change or interaction of a β1 integrin. In this morphologically structured system TGF‐β induced a number of subtle effects including formation of new extracellular matrix and conformational change of a β1 integrin, rather than the major quantitative changes in cell/matrix molecules reported previously.