bluuebunny/crossref_metadata_2025 huggingface dataset:
Chicken Major Histocompatibility Complex and Disease
Authors: HÁLA K. , BOYD R. , WICK G.
Published: June 2006

The chicken MHC (B complex) initially described by Briles as controlling blood antigens, is now known to be composed of at least three regions, L, F and G. Two of these, F and G, were described on the basis of recombinants found in a study of over 10,000 chickens. On the basis of biochemical, tissue distribution and functional analyses, F corresponds to the murine H‐2 K/D regions. The G region is unique to the chicken since the antigenic product is expressed only on erythrocytes and their progenitors. L was identified by serological studies and corresponds to the H‐2 I region; the L antigen is expressed predominantly on B lymphocytes, monocytes and 10% of T lymphocytes, and differences in the L region result in variations in immune responsiveness. A number of functional similarities exist between the chicken MHC and that of other species such as regulation of graft rejection, graft‐versus‐host reaction (GVHR) and mixed lymphocyte reactions (MLR), mitogenic and immune responsiveness and resistance to RNA and DNA virus infection. The chicken MHC also controls the severity of autoimmune disease, as exemplified by the spontaneous thyroiditis of Obese strain (OS) chickens. It differs from mammalian MHC's by having a lower crossing‐over frequency and no apparent gene duplication.
Evolutionary Relationship Between HLA‐DR Antigen β‐Chains, HLA‐A, B, C Antigen Subunits and Immunoglobulin Chains
Authors: LARHAMMAR D. , WIMAN K. , SCHENNING L. , CLAESSON L. , GUSTAFSSON K. , PETERSON P. A. , RASK L.
Published: June 2006

cDNA for a β‐chain of HLA‐DR antigens was cloned and the partial nucleotide sequence was determined. The data suggest that the β‐chain consists of approximately 230 amino acids, of which about 200 are exposed on the cell surface. The β‐chain appears to be composed of two exposed disulphide‐containing domains. The arrangement of the disulphide loops suggests that the β‐chain is similar in structure to the HLA‐A, B, C antigen subunits and the immunoglobulin chains. For the β‐chain domain closest to the membrane this similarity was verified at the level of primary structure. The partial amino acid sequence of the NH2‐terminal domain did not display any apparent homology to HLA‐A, B, C antigens and immunoglobulins. However, the similarity established here between the two types of major histocompatibility antigen subunits and the immunoglobulin chains suggests a common ancestral origin for at least some regions of these molecules.
Fact and Speculation on the Function of Immune Response Genes in Antigen Presentation
Authors: WERDELIN O.
Published: June 2006

Immune responsiveness of guinea pigs to dinitrophenyl‐poly‐l‐lysine and to the lysine rich random co‐polymer of l‐glutamic acid and l‐lysine are both controlled by a single gene, the ‘poly‐l‐lysine gene’. This paper reviews recent experiments which demonstrate that these two antigens specifically compete with one another for being presented to T cells by the same antigen‐presenting cells. This finding is interpreted to mean that antigens to which responsiveness is controlled by the same single gene compete for the Ir gene product of antigen‐presenting cells. The review discusses if the products of the immune response genes—presumably the Ia antigens—may constitute a third specific antigen recognition system. It further speculates if this idea may help to provide insight into the phenomenon of histocompatibility‐restriction and into the nature of the mixed leucocyte reaction.
In Vitro Enhancement of AA‐Degrading Activity in Human Plasma with the Plasminogen Activator Streptokinase
Authors: SKOGEN B. , NATVIG J. B.
Published: June 2006

Radiolabelled protein AA was coupled to cyanogen‐bromide‐activated Sepharose 6 MB and used as a substrate to determine the AA‐degrading activity of enzymes in solution. The applicability of the substrate was tested with an elastase preparation known to have AA‐degrading activity. The substrate was used to determine the AA‐degrading activity in fractions of normal human serum in the presence and absence of the plasminogen activator streptokinase. The AA‐degrading activity was increased in fractions in which streptokinase‐induced plasminogen activation had occurred. The increase in activity could be inhibited with antibodies to plasminogen. AA‐degrading activity could also be increased in whole human plasma by the addition of streptokinase.
Medial Histocompatibility Antigens
Authors: LINDAHL K.FISCHER , LANGHORNE J.
Published: June 2006

Medial histocompatibility (H) antigens are weak H antigens, recognized by unrestricted T cells; they differ thus from both major and minor H antigens. An example, Qed‐1, is described in detail, and other known medial H antigens of the mouse are reviewed. The structural and genetic relationships of major and medial H antigens and their role in T cell recognition are discussed.
The 5936 Ig‐Idiotype(s): Genetic Linkage to Ig‐CH Loci, T‐Cell Dependence of Synthesis and Possible Specificities
Authors: SUZAN M. , BONED A. , LIEBERKIND J. , VALSTED F. , RUBIN B.
Published: June 2006

5936‐idiotype(s) are defined by a rabbit antiserum which was obtained by immunizing a mouse‐immunoglobulin(MIg)‐tolerant rabbit 5936 with B6 anti‐CBA Ig from a single B6 mouse. These idiotypes were found on IgG1 molecules in sera from B6 mice immunized with cells carrying the IAk alloantigen, and they were associated with B6 Ig allotypes (Igh‐1b). The particular interest of this idiotypic system is that antiserum 5936 also detects idiotypes (Id) on B6‐T cells immunized in vitro with IAk alloantigen, and such T‐cell Id were found to be associated with Ig allotypes. We attempted to show that the 5936‐Id on Ig molecules were linked to Igh‐1b allotypes by backcross analysis. In addition, it was investigated whether the 5936‐Id response was a T‐cell‐dependent response, and, if so, whether there was any restriction in this T‐B cell collaboration. Finally, we continued our studies on the specificity of 5936‐Id+ Ig molecules.

The present experiments show that 5936‐Id are linked to Igh‐1b allotypes and that the quantity of 5936‐Id produced appears to be regulated by Ir genes in the H‐2 complex. The synthesis of 5936‐Id is T‐cell dependent, and only lgh‐1b allotype compatible T cells would collaborate with 5936‐Id+ B‐cell precursors. 5936‐Id+ Ig molecules appeared not to have specificity against eco‐ and xenotropic viruses. However, monoclonal antibodies produced from B6‐T‐cell‐reconstituted B6 nude mice may carry 5936‐Id and have specificity for B6‐T‐cell membrane molecules.

The relevance of these findings to the question of whether or not T and B cells display identical idiotypes are discussed.
The Mechanism of Graft Rejection and the Concept of Antigenic Strength
Authors: HOWARD J. C. , BUTCHER G. W.
Published: June 2006

‘It must be for almost ten years now that I have been stubbornly holding the view that the strength of transplantation antigens is essentially a direct function of the number of immunologically competent (antigen sensitive) cells which can recognize the antigen as foreign and react against it’. (Morten Simonsen, 1970 [13].)
The Still Elusive T Cell Receptor
Authors: JENSENIUS J. C. , CRONE M. , KOCH C.
Published: June 2006

The contention that VH constitutes a part of T‐cell receptors for antigens was probed by purifying rabbit T cells and analysing these cells for non‐immunoglobulin VH, i.e. VH not associated with L chain, A number of anti‐VH antisera were employed for this purpose, the most important being goat antiserum, reacting with common al allotype determinants (allotype determinants expressed on free VH and H chain as well as on intact immunoglobulins), rat antibody against common non‐allotype VH determinants (VH framework determinants expressed on VH and H chain as well as on intact immunoglobulins) and chicken antibody against unmasked non‐allotype determinants (VH determinants accessible only in the absence of L chain). VH and L chain was quantified by radioimmunoassays on extracts and supernatants from unstimulated T cells as well as from T cells stimulated by concanavalin A and by allogeneic cells. Absolute depletion of Ig‐containing and ‐producing cells was not achieved but in no case was an excess of VH over L chain observed. This indicates that all detected VH originated from cells of the B lineage. The cells were also cultured in the presence of labelled amino acids followed by analysis of detergent extracts and supernatants by immunoadsorption and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS‐PAGE) fluorography. Again, no evidence for T‐cell VH could be found. Affinity purified anti‐VH antibody was used to label viable rabbit T cells through the use of secondary fluorescence‐labelled anti‐immunoglobulin antibody. No VH‐specific labelling of T cells could be observed. Mixed lymphocyte cultures were carried out in the presence of affinity‐purified anti‐VH antibodies. No inhibition of the reaction could be discerned. The failure to detect T‐cell VH is in agreement with the recent finding that the VH‐genome in T cells is not rearranged in a functional manner similar to that in B cells.
The Stimulus to Host Cell Proliferation in Graft‐versus‐Host Reactions
Authors: FORD W. L. , ROLSTAD B. , FOSSUM S. , HUNT S. V. , SMITH M. E. , SPARSHOTT S. M.
Published: June 2006

Two experiments are described concerned with the mechanism of host cell activation in the rat popliteal lymph node (LN) undergoing a graft‐versus‐host (GVH) reaction. (1) Irradiated, F1 hybrid hosts (750 rad) mounted an impaired response to parental strain T cells. This was augmented by an intravenous injection of F1 hybrid lymphocytes but not by parental strain B lymphocytes syngeneic with the initiating T cells. When the donor T cells (footpad) und B lymphocytes (intravenous) were completely allogeneic the residual response of the irradiated F1 was completely inhibited. (2) The popliteal LN response in the semi‐allogeneic situation of the type (A × C)F1→(B × C)F1 was, if anything, weaker than in the allogeneic situation AA→BB. These results and other data are discussed in terms of a possible major histocompatibility complex (MHC) requirement for host cell activation. The sharing of an MHC haplotype between donor and host cells is unlikely to be a necessary or sufficient condition for host cell activation.
Mechanisms of Altered in Vitro Antibody Response in the Rat by a Small Synthetic Polymer
Authors: TEODORCZYK‐INJEYAN J. A. , MAKOWKA L. , FALK R. E. , FALK J. A.
Published: June 2006

NED 137, a low molecular weight synthetic polymer, enhances the rat humoral immune response to cellular antigens in vivo. The effect of NED 137 on the in vitro antibody response to sheep erythrocytes was studied in normal and macrophage‐depleted rat spleen cultures. The polymer stimulated the IgM antibody response of normal splenocytes, and its immunopotentiating activity was increased in macrophage‐depleted spleen cell preparations. NED 137 enhanced both the primary and the secondary plaque‐forming cell (PFC) response of rat splenocytes in a dose‐ and time‐dependent manner. This stimulatory effect of the polymer was dependent on the presence of antigen and demonstrated antigen specificity. The PFC and mitogenic responses of both normal and macrophage‐depleted rat splenocytes were dramatically inhibited in cultures prepared from animals pretreated with NED 137 before culture initiation. The antigen dependency, specificity and potentiation of a secondary response suggest that NED 137 acts through the triggering of the lymphoid system but not as a ‘conventional’ B‐cell polyclonal activator.
Epstein‐Barr Virus Increases the Proliferative Response and the Generation of Suppressor and Cytotoxic T‐Cell Functions in Autologous Mixed Lymphocyte Reaction
Authors: PALACIOS R.
Published: June 2006

Epstein‐Barr virus (EBV) infection of stimulator cells significantly increased the proliferative response of T cells in the autologous mixed lymphocyte reaction (AMLR). The addition of a monoclonal anti‐HLA‐DR antibody toAMLR cultures in which either EBV‐infected or non‐infected non‐T cells wereused as stimulator cells strongly inhibited the proliferative response irrespective of the presence of EBV. It is concluded that EBV does not by itself activate the responding cells and that HLA‐DR antigens are necessary to trigger T cells. Increased generation of suppressor T cells, determined in both alloantigen‐induced DNA synthesis and pokeweed‐mitogen‐stimulated immunoglobulin production, was found after an EBV infection of stimulator cells. Similarly, EBV‐infected non‐T cells significantly increased the generation of killer T cells, determined in three different types of target cells: phytohaemagglutinin‐stimulated mononuclear cells, EBV‐transformed cells, and con‐canavalin‐A‐activated murine spleen cells. The increased T‐cell responses after an EBV infection may reflect the attempts in vivo to control andhold in check the viral infection.
Hydrocortisone Abrogates Proliferation of T Cells in Autologous Mixed Lymphocyte Reaction by Rendering the Interleukin‐2 Producer T Cells Unresponsive to Interleukin‐1 and Unable to Synthesize the T‐Cell Growth Factor
Authors: PALACIOS R. , SUGAWARA I.
Published: June 2006

Hydrocortisone (HC‐A) inhibited the proliferative response in the autologous mixed lymphocyte reaction (AMLR). The inhibitory activity became apparent 48 h after initiation of the cultures and was maintained throughout the culture period. T cells from cultures treated with HC‐A showed a proliferative response to interleukin‐2 (IL‐2) of a similar degree as T cells from cultures not exposed to this drug. Hydrocortisone abrogated the production of IL‐2 in AMLR. The addition of interleukin‐1 (IL‐1) to HC‐A‐treated cultures did not restore or increase the synthesis of IL‐2, whereas IL‐1 added to non HC‐A‐treated cultures significantly enhanced the synthesis of IL‐2. Finally, IL‐2 but not IL‐1 could overcome the abrogatory effect of hydrocortisone on proliferation of T cells induced by AMLR. These results indicate that HC‐A inhibits proliferation of T cells in AMLR by causing the IL‐2 producer T cells to become unresponsive to IL‐1 and unable to synthesize IL‐2. This drug does not, however, interfere with the process by which resting T cells acquire responsiveness to IL‐2.
Studies on the Defect in Cell‐Mediated Immunity in Lepromatous Leprosy using HLA‐D‐Identical Siblings
Authors: STONER G. L. , MSHANA R.N. , TOUW J. , BELEHU A.
Published: June 2006

Sixteen healthy siblings were identified as HLA‐D‐identical to 12 borderline lepromatous or polar lepromatous leprosy patients by the absence of a mixed lymphocyte reaction (MLR). The peripheral blood mononuclear cells (PBM) of the healthy siblings showed a lymphoproliferative response (Δcpm) to Mycobacterium leprae antigens which was about fivefold or more greater than that of the lepromatous patients. Lepromatous PBM, with or without mitomycin C treatment, were co‐cultured with a constant number of normal PBM. In other experiments the two cell types were co‐cultured in various proportions, with the total cell number kept constant. Neither approach revealed suppressor cells in lepromatous PBM capable of suppressing the lymphoproliferative response to M. leprae. On the contrary, we found lhat lepromatous PBM can respond to M. leprae antigens if the sensitized lymphocyte is provided by mitomycin‐C‐treated normal PBM. Additionally, experiments in which isolated adherent cells and non‐adherent cells of sibling pairs were recombined failed to reveal a defect in the M. leprae antigen‐presenting function of lepromatous adherent cells. Since we found no evidence that sensitized cells are present in lepromatous PBM with their function unexpressed (due to a monocyte defect) or suppressed (due to suppressor cells), we conclude that lepromatous patients simply lack sufficient numbers of antigen‐specific T lymphocytes to initiate a lymphoproliferative response to M. leprae antigens. The reason for their absence remains an important unanswered question.
Rabbit Spleen B Lymphocytes as Helper Cells in Lymphocyte Activation by Concanavalin A and Phtyohaemagglutinin
Authors: CAVAILLON J.‐M. , UDUPA T. N. S. , CHOU C.‐T. , CINADER B. , DUBISKI S.
Published: June 2006

Using rosetting methods, we have purified rabit B cells and studied their interactions with T cells purified by passage over an anti‐immunoglobulin‐coated Degalan beads column. B cells enhance the responce of T cells in concanavalin A (Con A) and phytohaemagglutinin. In regulation of the response to Con A, an adherein cell is a third participating cell B‐cell preparations, contain a minority of cells that can respond to T mitogens with the help of non‐proliferating T cells, but the proportion of these responding cells is small, and the involvement of a T‐cell impurity cannot be excluded.
Studies on Human Epidermal Langerhans Cells
Authors: BRAATHEN L. R. , THORSBY E.
Published: June 2006

Epidermal cell suspensions were produced containing 3–6% HLA‐DR‐positive Langerhans cells. By using mixtures of epidermal cells and allogeneic T lymphocytes from donors sensitized to purified protein derivative of tuberculin (PPD) and herpes simplex virus (HSV), we could show that a proliferative in vitro response to these antigens, similar in strength to that seen in autologous combinations of macrophages or epidermal cells and T cells, could be obtained provided the epidermal cells shared both HLA‐D/DR determinants with the T‐cell donor. No antigen‐specific response was obtained in fully HLA‐D/DR‐disparate combinations. These results, together with previously reported data using other antigen‐presenting cells, further emphasize that one minimal requirement for antigen‐specific activation of T cells is co‐recognition of products of the self HLA‐D region.
A Solid‐Phase Radioimmunoassay for Anti‐Histone Antibodies in Human Sera: Comparison with an Immunofluorescence Assay
Authors: RUBIN R. L. , JOSLIN F. G. , TAN E. M.
Published: June 2006

A solid‐phase assay for anti‐histone antibodies is described, in which antibodies bound to calf thymus total histones, specific histone classes, or chromatin were detected by radioactive anti‐human IgG, IgA or IgM. The reactivity of human sera from various rheumatic diseases was analysed by this assay and compared with results obtained from an indirect immunofluorescence assay (FANA) previously described. Sera that were positive in the FANA assay were usually positive in the solid‐phase assay when total histones were the solid‐phase antigen. However, many sera had IgM antibodies to total histones in the solid‐phase assay but gave no detectable reaction in the FANA assay. Results from the solid‐phase assay, using individual histones and chromatin, showed that the anti‐histone antibodies in these sera were predominantly reactive with histones H3‐H4 and did not bind well to histones complexed to DNA in the form of chromatin.
V and C Genes in Creating Antibodies Directed to α(1→3)‐linked D‐Glucosyls in Dextran
Authors: BELL C.
Published: June 2006

An evaluation was made of the frequency of α(1→3)‐responsive, primary B precursors and their reactivity profiles in Igh‐la1 (al) and Igh‐lb(b) allogroup mice, of dissimilar responsiveness as to quantity of the specific serum antibody produced, its light chain isotype, and its variable‐region, ligand‐modifiable antigenicity, to α(1→3) glucosyls in dextran B‐1355. al mice, exhibiting high λ1‐specific serum antibody, with relatedness to the idiotypes (Id) shared by three BALB/c, α(1→3)‐specific, λ1 myeloma proteins, possess specific primary splenic B precursors at a frequency of 1/5.5–7.3 × 104 cells; b mice, exhibiting low, K serum, Id− antibody, possess B splenic‐specific primary precursors at a frequency of 1/1.0–1.4 × 105 cells. A radioimmunoassay analysis showed correlations between the isotype profiles of the serum antibody response and of the primary precursors, namely μγ1 in the al and μγ in the b allogroups, but also delineated minor primary μγλ1 and μγκ precursors in al and μγκ and μλ1 in b, at frequencies of 1/3 × 105 to 1/6.5 × 106. The al, λ1 precursors exhibited defined reactivity patterns for 3‐mono‐O‐3,6‐di‐O‐glucosyls and non‐reducing end groups in the B‐1355. The b, K precursors recognized the sequential residues.
Concanavalin A Induces Suppressor Cell Activity in Both TgM and Tnon‐γ Cells: Most of the Suppressor Cells Do Not Carry HLA‐DR Antigens
Authors: DOBLOUG J. H. , FØRRE O. , CHATTOPADHYAY C. , NATVIG J. B.
Published: June 2006

Concanavalin A (Con A) stimulation of T lymphocytes for 48 h induced a dose‐dependent increase in the percentage of Tγ cells, and proliferation of these cells was dependent on pre‐existing Tγ cells. Con A stimulation also induced a dose‐dependent increase in suppressor cell activity as measured in a Con A/mixed lymphocyte culture assay. Removal of Tγ cells before stimulation with Con A did not influence suppressor cell activity, whereas depletion of Tγ cells after Con A stimulation significantly reduced the suppression. Treatment of T lymphocytes with monclonal anti‐HLA‐DR antibodies and complement significantly increased the percentage of Tγ cells and also increased the suppressor cell activity, both when the cells were treated before and when they were treated after Con A stimulation. Similarly, increased suppressor cell activity was also seen when Tγ cells were removed. The results indicate that Con‐A‐induced suppressor cells are recruited from both Tγ and Tnon‐γ cells and also suggest that most of the Con‐A‐induced suppressor cell activity is exerted by HLA‐DR‐negative cells.
Effects of nu Gene on the Numbers of Mast Cells in Lymph Nodes
Authors: WLODARSKI K. , MORRISON K. , ROSE N. R.
Published: June 2006

The total numbers of masl cells (MC) in popliteal lymph nodes of homozygous nude (nu/nu) and phenolypicaily normal, heterozygous (+/nu) BALB/c mice are greater than in normal (+/+) BALB/c mice at approximately 6 months of age. The values obtained from 4‐ to 7‐month‐old (nu/nu) and (+/nu) mice are twice as high as those from 2‐ to 3‐month‐old mice. It is concluded that the thymus does not directly determine the number of MC in lymph nodes, but the presence‐of the nu gene or another gene closely linked to the nu gene regulates the number of MC.‘Nude’ mice infected with hepatitis virus accumulate many more MC than do healthy mice.
Modulation of the Immune Response by Plasma Protease Inhibitors
Authors: ADES E. W. , HINSON A. , CHAPUIS‐CELLIER C. , ARNAUD P.
Published: June 2006

The two major protease inhibitors in human serum, alpha1‐antitrypsin (α1AT) and alpha2‐macroglobulin (α2m), were analysed for their effects on antibody‐dependent cell‐mediated cytotoxocity (ADCC) and natural killing (NK). The results indicate that both α1AT and α2m decrease ADCC and NK in a dose‐responsive pattern.
Modulation of the Immune Response by Plasma Protease Inhibitors
Authors: GRAVAGNA P. , GIANAZZA E. , ARNAUD P. , NEELS M. , ADES E. W.
Published: June 2006

In two different cytolytic assays, dose‐dependent inhibition of antibody‐dependent cellmediated cytotoxicity and natural killing by alpha2‐macroglobulin (α2m) and its subunits was observed. α2m subunits were approximately four times more inhibitory in both assays than the native 2m molecule on a molar basis. Analysis of trypsin protein esterase activity demonstrated that α2m subunits were four times more active than the parent molecule.
Induction of E‐Rosette‐Promoting Factor in Human Plasma by Levamisole: An Assessment in a Patient with Partial DiGeorge Syndrome
Authors: SEKI H. , YOKOI T. , KUBO M. , MORIYA N. , MIYAWAKI T. , NAGAOKI T. , MIURA M. , TANIGUCHI N.
Published: June 2006

A male infant with partial DiGeorge syndrome responded to weekly administration of levamisole (2.5 mg/kg of body weight) with an increase of circulating E‐rosette‐forming T cells. Thymic hormone activity in plasma appeared to be elevated to a near‐normal level of 11.6 ng thymopoietin equivalent/ml after levamisole administration. The in vitro incubation studies indicated that levamisole by itself had no E‐rosette‐promoting ability, but a dialysable and relatively heat‐stable plasma factor induced by levamisole both in the patient and in heallhy individuals had E‐rosette‐promoting activity for the patient's lymphocytes. Such a plasma factor, however, could not be induced in all four thymectomized myasthenic subjects examined, suggesting a thymus‐dependent nature of the plasma factor. These results suggest that levamisole might mediate an increased secretion of humoral factor(s) with E‐rosette‐promoting activity, even from such a rudimentary thymus as in the partial DiGeorge syndrome.
Natural Killer Cells Do Not Belong to the Recirculating Lymphocyte Population
Authors: ZÖLLER M. , BELLGRAU D. , AXBERG I. , WIGZELL H.
Published: June 2006

Natural killer (NK) cells constitute a cell type with an as yet undefined lineage, although certain similarities with T lymphocytes have been found in the mouse. Our present results show that NK cells have a significant difference compared with T and B cells in their capacity to traverse the blood‐lymph barrier. Thoracic duct lymphocytes from mice or rats are thus devoid of NK activity, when at the same time potential, cytotoxic T lymphocyte (CTL) activity or antibody‐dependent cellular cytotoxicity function can be demonstrated. Chronic thoracic duct drainage in the rat also leads to an increase in NK activity per unit cell number in the other lymphoid organs. Thoracic duct lymphocytes from mice and rats may thus serve as convenient sources of CTL and/or killer cells in situations in which it is important to minimize NK cell involvement.
Endocytosis of Agarose in Mouse Peritoneal Macrophages in Vitro
Authors: JOHNSON E. , SELJELID R. , BØGWALD J. , LARM O. , SCHOLANDER E.
Published: June 2006

We have studied the endocytosis of tritium‐labelled and of non‐radioactive agarose in mouse macrophages in vilro. The endocytosis was greatest and most rapid in syngeneic mouse serum and in human serum, reaching a plateau after 12 h of incubation. Ten per cent serum was the minimum concentration giving optimal ingestion. The endocytosis appeared to be regulated by mechanisms involving complement factors C3 and B. Different pretreatments of sera, inactivating or depleting C3 and B, resulted in 70–80% reduction of endocytosis, Preincubation of agarose in untreated serum increased the endocytosis of agarose in heat‐inactivated serum three‐fold, indicating that the essential factors were bound to agarose. Antibodies against C3 and B reduced endocytosis moderately hut significantly.
Induction of a Metallothionein‐like Protein in Human Lymphocytes
Authors: ALEXANDER J. , FØRRE Ø. , AASETH J. , DOBLOUG J. , ØVREBØ S.
Published: June 2006

Human peripheral lymphocytes were cultured in the presence of low (4μM) and high (100, 150 (μM) concenrations of zinc. Lymphocytes stimulated with phytohaemagglutinin (PHA) or tuberculin (PPD) synthesized metallothionein only in the presence of high concentrations of Zinc ions. Presence of a high zinc ion concentration alone did not stimulate the synthesis of DNA or of rnetallotnionein.
Detection of T‐Lymphocyte Subpopulations in the Peripheral Blood and the Synovium of Patients with Rheumatoid Arthritis and Juvenile Rheumatoid Arthritis Using Monoclonal Antibodies
Authors: FØRRE Ø. , THOEN J. , DOBLOUG J. H. , EGELAND T. , KVIEN T. K. , MELLBYE O. J. , NATVIG J. B.
Published: June 2006

Monoclonal antibodies with specificities for various human T‐cell antigens were used in direct immunofluorescence to quantify the proportions of T lymphocytes with suppressor/ cytotoxic‐cell markers and with helper/inducer‐cell markers and of T lymphocytes with HLA‐DR antigens. Normal percentages of lymphocytes with suppressor/cytotoxic‐cell markers were detected in the peripheral blood synovial fluid and synovial tissue lymphocytes from patients with juvenile rheumatoid arthritis (JRA) and rheumatoid arthritis (RA), respectively. Normal percentages of T lymphocytes with helper/inducer‐cell markers were seen in the peripheral blood of RA and JRA patients and in the synovial tissues of RA patients. Slightly decreased percentages of cells with the helper/inducer‐cell marker were detected in the synovial fluids of JRA patients. The proportions of HLA‐DR‐positive T lymphocytes were highly increased in the synovial fluid and synovial tissue, whereas the numbers of these cells in the peripheral blood were normal. No significant differences in Tγ cells were detected between peripheral blood, synovial fluid and synovial tissue of JRA patients or between peripheral blood and synovial tissue of RA patients.
Interleukin‐2 and Serum Thymic Factor Enable Autologous Rosette‐forming T Lymphocytes to Generate Helper and Cytotoxic Functions
Authors: SUGAWARA F. , PALACIOS R.
Published: June 2006

The autologous rosette‐forming T cells (Tar cells) isolated by means of their ability to form rosettes with autologous erythrocytes were characterized by the use of OKT monoclonal anti‐human T‐cell subset antibodies and a monoclonal anti‐HLA‐DR antibody. We found that the phenotype of Tar cells was OKT 3+4+8+Dr− as determined by both indirect imnrunofluorescence microscopy and complement‐mediated killing of 51Cr‐labelled Tar cells. In addition, we found that Tar lymphocytes were able to develop cytotoxicity against allogeneic and trinitrophenol (TNP)‐conjugated autologous target cells in the presence of interleukin‐2 (IL‐2) or serum thymic factor. However, these cells showed little or no cytotoxicity in the absence of interleukin‐2 or serum thymic factor. Tar lymphocytes generated helper function for B lymphocytes in the presence of interleukin‐2 in both pokeweed mitogen (PWM)‐ and purified protein derivative (PPD)‐stimulated cultures. Nevertheless, non‐IL‐2‐treated Tar cells did not exhibit any helper activity on B cells. Finally, pretreatment of Tar cells with 1000–1500 rad of X ray made these cells unable to develop helper function for B lymphocytes. It is concluded that: (1) OKT 3+4+8+Dr− Tar cells are able to generate cytotoxicity against alloantigens and TNP‐labelled self structures provided they are stimulated by IL‐2 or serum thymic factor; (2) these cells need both to proliferate and to receive help from IL‐2 to develop helper cells capable of assisting B‐lymphocyte differentiation into plasma cells in both PWM‐ and PPD‐stimulated cultures.
Immunological Tolerance in the Chicken
Authors: RODRICK M. L. , MORGAN E. L. , TEMPELIS C. H.
Published: June 2006

Two soluble non‐specific supprcssive factors were isolated by gel chromatography from the serum of chickens tolerant to bovine serum albumin (BSA). Fraction I was found by sodium dodecyl sulphate‐polyacrylamide gel electrophoresis (SDS‐PAGE) to contain five proteins with moi. wts from 200,000 to 900,000 unreduced and six proteins that ranged from 70,000 to 180,000 when reduced. The composition was primarily protein, with a small amount of carbohydrate and lipid. One component was identified as IgM, one as a lipoprotein. The others remain unidentified. No evidence of the tolerogen, BSA, was found. The second factor, fraction III of both (olerant and normal serum, was found by SDS‐PAGE to have two proteins with mol. wts of 54,000 and 78,000 in the unreduced form and contained a very small amount of protein, a large amount of carbohydrate, and no detectable lipid, Normal fraction III had two proteins with mol wts of 54,000 and 65,000 when reduced, whereas reduction did not affect tolerant fraction III. A soluble suppressive factor, secreted by cultured adherent cells of tolerant chickens, was found to be comparable to fraction III in molecular weight. Comparison of these results with those of other reported suppressive factors is made and possible identities of the suppressive components of fractions I and II are discussed.
Polyclonal Activation of Human Peripheral Blood B Lymphocytes by Formaldehyde‐Fixed Salmonella paratyphi B
Authors: CHEN W.‐Y. , FUDENBERG H. H. , ADES E. W.
Published: June 2006

B‐cell ‘activation’ in cultures stimulated with pokeweed mitogen (PWM), Staphylococcus aureus strain Cowan I, or formaldehyde‐fixed Salmonella paratyphi B (SPB) was evaluated by enumeration of cells secreting immunoglobulin (Ig) and by quantitation of Ig released into culture supernatants. A dissociation between these two values was found after day 6 in cultures activated with PWM or SPB, suggesting that Ig‐secreting cells (ISC) are heterogeneous in terms of Ig secretion rate. Generation of ISC in cultures activated with PWM or SPB was partially inhibited by hydroxyurea, but [g levels in culture supernatants were not affected. These results indicate that there are at least two subpopulations of ISC in stimulated peripheral blood lymphocyte cultures, one sensitive to, and the other resistant to, hydroxyurea. The hydroxyurea‐resistant subpopulation appeared to be more mature and to release almost all of the Ig detected in culture supernatants. Furthermore, time‐course studies of ISC numbers and Ig levels showed that each ISC in SPB‐stimulted cultures (but not in PWM‐stimulated cultures) was more active in Ig synthesis and secretion after day 8 than before day 6, indicating that after day 8 most of the ISC in cultures activated with SPB were hydroxyurea‐resistant. These studies suggest that SPB is another useful polyclonal B‐cell ‘activator’ for studies of human B‐cell differentiation and function, and that SPB defines two distinct subsets of B cells.
Cytotoxicity of Tumour‐Bearer Serum to D23 Hepatoma Cells Derived from Solid Tumours, Ascites or in Vitro Cultures
Authors: LANDO P. , GABRIEL J. , BERZINS K. , PERLMANN P.
Published: June 2006

The complement‐dependent cytoloxicity of antibodies in tumour‐bearer serum (TBS) from rats carrying the chemically induced D23 hepatoina was investigated. Target cells were D23 cells from solid tumours (D23sol), from ascites tumours (D23asc), or from in vitro growing cell cultures (D23cc). The D23asc and D23cc cells were not lysed when used as target cells in the assay, although they evoke cylotoxic antibodies when growing in vivo. The D23 ascites cells became susceptible to complement‐dependent lysis after trypsin treatment. This was, however, not due to unmasking of target antigens, since untreated D23 ascites cells absorbed cytoloxic antibodies as efficiently as trypsinized cells. No increase in susceptibility to complement‐dependent lysis was observed after trypsin treatment of D23cc cells. Absorption of cytotoxic antibodies with D23cc cells showed no or very low antigen expression on the surface of these cells. They did, however, contain the antigen(s), since 3 m KCI extracts of the D23cc cells could inhibit the complement‐dependent cytoloxicity of D23sol TBS against D23sol cells. From these data it was concluded that the susceptibility of hepatoma cells for antibody‐mediated complement lysis is not only correlated with antigen expression, as was the case with the in‐vitro‐cultivated cells, but is also dependent on increased lylic susceptibility after trypsin treatment of the cells.
Monoclonal Human B Lymphoma Cells Respond by DNA Synthesis to Anti‐Immunoglobulins in the Presence of the Tumour Promotor TPA
Authors: GODAL T. , HENRIKSEN AA. , RUUD E. , MICHAELSEN T.
Published: June 2006

Monoclonal human B lymphoma cells were triggered in vitro to DNA synthesis with F(ab')2 fragments of rabbit IgG antibodies specific for different human immunoglobulin (Ig) light and heavy chains. The specificity of the responses corresponded to surface Ig (sIg) present on tumour cells. Anti‐μ chain. anti‐δ chain, anti‐γ chain, and antibodies to light chains were found to mediate this effect. However, to induce DNA synthesis, the tumour promoter 12‐O‐tetradecanoyl‐phorbol‐13‐acetatc (TPA) was usually required. TPA alone induced cytoplasmic protrusions and increases in cellular volume. These observations should provide new opportunities to study the triggering of B cells with anti‐Ig in well‐defined cell populations.
Staphylococcal Protein A and Human IgG Subclasses and Allotypes
Authors: VAN LOGHEM E. , FRANGIONE B. , RECHT B. , FRANKLIN E. C.
Published: June 2006

Staphylocoecal protein A binds molecules belonging to the IgGl, IgG2, and IgG4 sub‐classes. IgG3 proteins generally do not bind, except for those coded by the two γ3 alleles, which are G3m(u−): G3m(b0,b3,b5,s,v) and G3m(b0,b3,b5,s,t,v). G3m(u) is located in the CH2 domain. The difference between G3m(u−) and G3m(u+) IgG3 proteins correlates with the sequence at position 339 in the CH2 domain—Ala and Thr respectively. There is another structural difference in the CH3 domain which correlates with protein A binding and non‐binding: all IgG proteins that bind protein A have His at position 435, whereas those that do not, have Arg at that position.
Impaired Proliferative Response to B‐Lymphocyte Activators in Common Variable Immunodeficiency
Authors: CUNNINGHAM‐RUNDLES S. , NGHAM‐RUNDLES C. CUNNI , MA D. I. , SIEGAL F. P. , GUPTA S. , SMITHWICK E. M. , KOSLOFF C. , GOOD R. A.
Published: June 2006

The cell‐mediated immune responses of 39 patients with common variable immunodeficiency (CV1) were studied in vitro, using Staphylococcus aureus and Escherichia coli prepared as whole cells and Candida albicans extract. These microbial activators were found to require intact B‐lymphocyte function for normal proliferative response. The patient group was observed to have significantly depressed lymphocyte responses compared with those of controls studied in parallel (P<0.01). Negative lymphocyte response to one activator and strongly positive response to another were found in individual patients. Examination of patients’ lymphocyte response to S. aureus and E. coli in association with serum IgG levels demonstrated that a rough correlation could be drawn, showing that patients with serum IgG < 125 mg/dl had markedly lower (P<0.01) lymphocyte responses than those with serum IgG > 300mg/dl. No similar correlation with phytohaemagglutinin activation was observed. Since depressed lymphocyte responses did not correlate with reduced B‐cell number in these patients, intrinsic B‐lymphocyte deficiency was indicated. These preparations of microbial activators are potentially useful tools in exploring lymphocyte subpopulation functions in primary immunodeficiency diseases.
Protein A Reactivity of Lymphocytes from Some Patients with Chronic Lymphocytic Leukaemia Mediated by an Interaction with the F(ab')2 Region of Surface Immunoglobulin
Authors: ROMAGNANI S. , GIUDIZI M. G. , BIAGIOTTI R. , GOGNA F. ALMERI , DEL PRETE G. F. , MAGGI E. , RICCI M.
Published: June 2006

Peripheral blood lymphocytes (PBL) from 15 of 38 patients with chronic lymphocytic leukaemia (CLL) were capable of forming rosettes with human erythrocytes coated with staphylococcal protein A (SpA‐HRBC). PEL from seven patients also showed a marked proliferafive response after stimulation with Staphylocccus aureus bacteria strain Cowan I (Cowan Staph). The SpA‐rosetling of CLL cells was inhibited by incubation with F(ab')2 fragments of anli‐immimoglobuiin (Ig) antibodies. In addition, incubation with these fragments inhibited the proliferative response of leukacmie B cells to Cowan Staph. The Cowan‐Siaph‐induced proliferation of CLL cells was also impaired by the addition of normal human IgG and human IgG F(ab')2 fragments to the cultures, whereas non‐immune rabbit IgG was not inhibitory, The inhibitory activity of human IgG F(ab')2 fragments was retained hy a SpA‐Sepharose column, and it was found in the material recovered from the same column by acid elution. These data indicate thai an interaction between SpA and a structure located in the F(ab')2 region of surface Ig of different classes is responsible for either SpA‐binding or the Cowan‐Staph‐induced proliferate response of PBL from some patients with CLL.
The Cytotoxic Effect of Mouse Macrophages Stimulated in Vitro by a β‐1,3‐d‐Glucan from Yeast Cell Walls
Authors: BÖGWALD J. , JOHNSON E. , SELJELID R.
Published: June 2006

Macrophages stimulated by an insoluble β‐1,3‐d‐glucan from yeast cell walls were able to destroy tumour cells as measured hy the release of radioactive label from prelabelled 14C‐thymidine cells. Target cells were B‐16 melanoma. P‐815 rrmstocytoma, and the L‐929 cell line, A significant target cell killing by macrophages stimulated by glucan was observed after 72–96 h. The cytolysis of L‐929 cells was investigated in some detail. No stable soluble cytolytic factor appeared to be released into the medium during the stimulation of macrophages by glucan. since cell‐free spent medium had no cytotoxic effect on L‐929 cells. The densities of the macrophage monolayers were critical for an effective target cell killing; dense cultures showed more cyioioxicity than less dense cultures. The kinetics of the development of macrophagc‐mediated cytotoicit suggests a minimum stimulation period of 4 days for maximal cylolysis.
Enhancement of in Vitro Immune Responses of Murine Peyer's Patch Cultures by Concanavalin A, Muramyl Dipeptide and Lipopolysaccharide
Authors: KIYONO H. , McGHEE J. R. , KEARNEY J. F. , MICHALEK S. M.
Published: June 2006

Immunofluorcscent and esterase staining of Peyer's patch (PP) cell preparations from six mouse strains showed that each strain possessed approximately eqtial numbers of T and B cells but less than 1% esterase‐positive cells (macrophages; Mψ). The addition of concanavalin A (Con A) to either lipopolysaccharide (LPS)‐responsive C3H/HeN or LPS‐non‐responsive 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‐rcsponsive (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 bntanol‐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 Mψ, 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 Mψ did not promote adjuvant responses. LPS(Ph) augmentation of immune responses required that Mψ (spleen) and PP cultures be derived from LPS‐re‐sponsive 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 Mψ for augmentation of immune responses.
Serodiagnosis of Syphilis by an Enzyme‐Linked Immunosorbent Assay for IgG Antibodies Against the Reiter Treponeme Flagellum
Authors: PEDERSEN N. STRANDBERG , PETERSEN C. SAND , VEJTORP M. , AXELSEN N. H.
Published: June 2006

An enzyme‐linked immunosorbent assay for IgG antibodies against the flagellum (axial filament) of the Reiter treponeme (flagellum‐ELISA) was developed and compared with the fluorescent treponemal antibody absorption (FTA‐ABS) test and the Treponema pallidum immobilization (TPI) test with regard to diagnostic sensitivity and specificity. One serum from each of 827 individuals with and without syphilis was studied. In all diagnostic groups of syphilis there was no significant difference between the sensitivity of the FTA‐ABS and the flagellum‐ELISA, except in treated syphilis, where the FTA‐ABS was more sensitive (P<0.01). In primary syphilis and in treated syphilis the sensitivity of the flagellum‐ELISA was higher than the sensitivity of TPI (P<0.01 and P≤0.05, respectively); in all other groups there was no significant difference between the sensitivity of TPI and flagellum‐ELISA. The specificity of the flagellum‐ELISA (99.0%) in 200 sera from blood donors without syphilis was not statistically different from the specificity of FTA‐ABS (98.0%) and TPI (99,5%). The flagellum‐ELISA seems to be well suited for routine serodiagnosis of syphilis and may replace other treponemal tests.
Intestinal Glycoprotein Activates the Alternative Complement Pathway by Reacting with Factor H
Authors: WINSNES R. , LACHMANN P. J.
Published: June 2006

Previous observations indicating complement activation via the alternative pathway of chelaled human serum by a rat intestinal glycoprotein fraction were substantiated by using C2‐deficient serum. Some inactivation of C6 by the glycoprotein was observed both in normal and C2‐deficient serum. As estimated by conglutination, the glycoprotein largely abolished the ability of serum to convert EAC3b to EA3Cbi, indicating inhibition of the control factors H (β1H globulin) and I (C3bINA), or inhibition of C3b deposition on the cells. The glycoprotein caused no change in the electrophoretic mobility of factors H or I. By immunoelectrophoresis the glycoprotein interfered with the precipitation line of plasminogen and β‐lipoprotetn and some other serum proteins. The absence of plasminogen or β‐lipoprotein in serum seemed unimportant for the C3 conversion by the glycoprotein. Factor H was retained when heal‐inactivated serum, heat‐inactivated serum depleted of 99% albumin or 85% IgG, or heat‐inactivated hypogammaglobulinaemic serum was eluted through a column of the intestinal glycoprotein coupled to epoxy‐activated Sepharose 6B. Presence of EDTA abolished factor H retention. Factor H from methylamine‐treated serum was also adsorbed to the glycoprotein. When serum depleted at 5°C of 31% of the factor H content was healed, the alternative pathway was activated spontaneously. Addition of some of the previously removed factor H reduced the O and factor B conversion rate.
Reduced Natural Killer Cell Activity of Lymphocytes from Patients with Werner's Syndrome and Recovery of Its Activity by Purified Human Leucocyte Interferon
Authors: GOTO M. , TANIMOTO KIYOAKI , HORIUCHI Y. , KUWATA T.
Published: June 2006

Natural killing (NK) activities were measured in peripheral blood lymphocytes (PBL) from 14 patients with Werner's syndrome (WS), and the results were compared with those of 187 normal individuals at different ages. The NK activities of healthy donors were demonstrated in a characteristic and invariable manner in accordance with the age and the sex, whereas the activities of WS patients were considerably reduced irrespective of the age and the sex. When normal PBL were preincubated with WS sera containing anti‐lymphocyte antibodies (ALA) plus rabbit complement, the NK activities of the surviving PBL were markedly reduced when compared with those of PBL treated with other heterologous ALA of rabbit origin in the same manner. PBL from WS patients treated with purified human leucocyte interferon augmented the NK activity even beyond the range of controls. These results suggested that NK activities in WS patients were reduced in a manner similar to that in normal old individuals. The ALA reactive to NK cells in WS patients may participate in the reduction of NK activities. The augmentative effect of interferon on NK activities in WS patients may also suggest the possible blocking of potent NK activities by an unknown mechanism rather than an intrinsic defect of their NK cells.