bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of the H-2 complex in induction of T helper cells in vivo. II Negative selection of discrete subgroups of T cells restricted by I-A and I-A/E determinants.
Authors: Sprent J , Alpert B
Published: June 2004

Previous studies have shown that negative selection of T cells to sheep erythrocytes (SRC) after adoptive transfer to irradiated mice requires a sharing of H-2 determinants between the donor T cells and the selection hosts. This paper examines which part of the H-2 complex controls selection. The results show that, in the case of T cells of the H-2k haplotype, complete selection occurs with donor host matching limited to the I-A through I-E subregions of the H-2 complex. Selection to SRC was partial in I-A compatible, I-E incompatible hosts, minimal or not detectable in I-A incompatible, I-E compatible hosts, but near-complete in hosts matched at both the I-A and I-E subregions. Consecutive selection in hosts matched solely at (a) the I-A subregion and (b) the I-E subregion led to incomplete selection. From these and other findings it is argued that H-2k T cells comprise a mixture of T cells restricted by I-A and I-A/E hybrid molecules.
Quantitative studies on T cell diversity. II. Determination of the frequencies and Lyt phenotypes of two types of precursor cells for alloreactive cytotoxic T cells in polyclonally and specifically activated splenic T cells.
Authors: Goronzy J , Schaefer U , Eichmann K , Simon M M
Published: June 2004

Two different limiting dilution systems have been applied to compare precursor frequencies of alloreactive cytotoxic T cells (CTL-P) in the polyclonally and specifically activated lymphocyte populations and in selected Lyt T cell subsets. Both systems make use of T cell growth factor for T cell expansion but differ with respect to the activation step in that lymphocytes are either activated directly with allogenetic stimulator cells or are sensitized polyclonally with concanavalin A (Con A) in bulk culture before their expansion under limiting dilution conditions. In polyclonally activated C57BL/6 lymphocyte populations, two types of CTL-P specific for H-2d alloantigens could be identified: a frequent set with a frequency of 1/100-1/300, and a rare set with a frequency of 1/2,000-1/8,000. In contrast, only a single CTL-P set was found in specifically activated populations with a frequency similar to that of the frequent CTL-P found on Con A blasts. In Con A blasts, the frequent at higher cell concentrations by suppressor T cells, whereas rare CTL-P were insensitive to this suppressive mechanism. Whereas in specifically activated T cells, the predominant CTL-P phenotype was Lyt-123, the predominant Lyt phenotypes for the frequent and the rare CTL-P found in Con A blasts were Lyt-123 and Lyt-123, respectively, which suggests that they represent primary and secondary CTL-P, respectively. The results are discussed with respect to previous reports on the involvement of Lyt T cell subsets in the generation of cytotoxic responses and their regulation by T suppressor cells.
Immunoglobulin-sulfated polysaccharide interactions. Binding of agaropectin and heparin by human IgG proteins.
Authors: Levy D E , Horner A A , Solomon A
Published: June 2004

The interaction of immunoglobulins with certain acidic polysaccharides was demonstrated by the binding of the sulfated glycans agaropectin and heparin by certain human IgG proteins. Heparin-binding IgG proteins can distinguish between the molecular forms of heparin derived from porcine intestine, bovine lung, and rat skin. The major specificity of these proteins is for native and certain high molecular weight subunit components of rat skin heparin. The interactions with multi-chain and single chain rat skin heparin are stable under physiological conditions and involve the Fab and, more specifically, the Fv region of the IgG molecule. These reactions occur as a result of an electrostatic interaction between cationic sites on certain IgG proteins and anionic sulfate resides of agaropectin or heparin. The characteristics of heparin-IgG interaction resemble those of heparin with other plasma proteins, the interactions of which have biological significance.
Polyspecific monoclonal lupus autoantibodies reactive with both polynucleotides and phospholipids.
Authors: Lafer E M , Rauch J , Andrzejewski C , Mudd D , Furie B , Furie B , Schwartz R S , Stollar B D
Published: June 2004

Hybridomas the produce anti-DNA autoantibodies were prepared from spleen cells of unimmunized MRL/1 mice, a strain that spontaneously develops severe systemic lupus erythematous (SLE). Reactivities of these monoclonal antibodies with a wide range of polynucleotides prompted tests of their reactions with phospholipids which, like polynucleotides, contain diester-linked phosphate groups in their backbones. In competitive radioimmunoassays, cardiolipin, phosphatidic acid, and phosphatidyl glycerol blocked the binding of these hybridoma antibodies to denatured DNA. These phospholipids also specifically inhibited the reaction between a hybridoma antibody and a site-specific anti-idiotypic antibody. The antinuclear reaction of one of these antibodies was specifically inhibited by cardiolipin. This same antibody prolonged the activated partial thromboplastin time in a manner characteristic of a lupus anticoagulant, presumably by binding to phospholipid in the test system. The polyspecific reactivity of a single molecular species of lupus autoantibody suggests that some of the diverse serological abnormalities of SLE may be a result of the binding of certain autoantibodies to a phosphodiester-containing epitope that is present in diverse biological molecules.
Idiotype-anti-idiotype regulation. I. Immunization with a levan-binding myeloma protein leads to the appearance of auto-anti-(anti-idiotype) antibodies and to the activation of silent clones.
Authors: Bona C A , Heber-Katz E , Paul W E
Published: June 2004

BALB/c mice immunized multiple times with ABPC48 (A48 or Ab1), a BALB/c bacterial levan (BL)-binding myeloma proteins, produce anti-Ab1 antibodies (Ab2). Immunization with only tow doses of AB1 often leads to the production of anti (antiA48) (Ab3) as does immunization with hemocyanin conjugates of Ab2. Finally, immunization with hemocyanin conjugates of Abf3 leads to the production of anti- (anti-[anti-A48]) (Ab4). Normal BALB/c mice immunized with BL produce an anti BL antibody response containing no detectable Ab1 idiotype (Id)-bearing molecules. Mice producing Ab3 express substantial amounts of Ab1 Id in their anti-BL response whereas mice producing Ab2 and Ab4 show a generalized inhibition in their anti BL response. These results indicate that states of immunity within an idiotypic chain may have marked effect on antibody responses to the antigen (i.e., BL) which is the putative initiator of the chain. Strikingly, the chain itself has an interesting feature. That is, Ab3 and Ab1 share a cross-reactive Id in that both are bound by Ab4 and Ab2. We propose a model of Id-anti-Id systems to explain this unexpected result. This is based on the concept of regulatory idiotopes on Ab1 molecules which initiate Ab2 (anti-idiotope) responses. In contrast, Ab2 molecules generally fail to initiate anti-Ab2 Id responses eigher because any individual idiotope is present at very low concentration or because Ab2 molecules tend to lack regulatory idiotopes. Thus, Ab2 molecules immunize syngeneic animals because they interact with cells bearing Ab1 like regulatory idiotopes. Thus, Ab3 will share regulatory idiotopes with Ab1. Ab4 and Ab2 will share the ability to bind the Ab1-like regulatory idiotope.
Major histocompatibility complex restriction of soluble helper molecules in T cell responses to altered self.
Authors: Plate J M
Published: June 2004

Evidence for major histocompatibility complex (MHC) restriction of soluble helper effects was observed in the generation of syngeneic killer T cells to trinitrophenyl-altered self. Ia-bearing T cells obscure the observation of such interactions, thus, must be removed to detect MHC restriction of nonspecific soluble helper factor supernates (HFS). Genetic mapping studies demonstrated that the strain producing HFS must be compatible in the H-21A region with the strain utilizing the helper molecules for optimal helper signals to be delivered.
Susceptibility of leishmania to oxygen intermediates and killing by normal macrophages
Authors: Murray HW
Published: June 2004

This study demonstrates that the promastigote form of virulent Leishmania donovani and Leishmania tropica are both deficient in endogenous enzymatic scavengers of H(2)0(2) (catalase, glutathione peroxidase) and susceptible to low fluxes of H(2)O(2) in a cell-free model. In addition, the killing of promastigotes by H(2)0(2) is markedly enhanced in the presence of a peroxidase and halide. Promastigotes also readily trigger the macrophage oxidative burst including the generation of H(2)0(2), and most intracellular promastigotes are killed within 18 h by unstimulated normal resident cells. Catalase, but not scavengers or quenchers of O(2)(-), OHx, or (1)O(2), protected promastigotes in a cell-free xanthine oxidase microbicidal system, and catalase also partially inhibited the leishmanicidal activity of resident macrophages. Thus, amongst various oxygen intermediates, H(2)0(2) alone appeared to be both necessary and sufficient for promastigote killing. Depriving macrophages of exogenous glucose, which inhibits the generation of oxygen intermediates, achieved effects similar to catalase treatment. These observations directly contrast with the intracellular parasite, T. gondii which is richly endowed with catalase and glutathione peroxidase, highly resistant to H(2)0(2), and requires products of O(2)(-)-H(2)0(2) interaction for effective oxidative killing. Toxoplasmas also fail to trigger the respiratory burst of normal macrophages, and readily multiply within these cells (1-5). Macrophages first activated by in vivo or in vitro immunologic stimuli, however, display an enhanced capacity to generate oxygen intermediates beyond O(2)(-) and H(2)0(2), and are able to kill toxoplasmas or inhibit their intracellular replication (1, 2).

These studies illustrate the wide spectrum of susceptibility to oxidative products which appears to exist for virulent intracellular protozoans, and indicate that such differences may be reflected in contrasting fates of parasites within cell-free oxidative environments and the cytoplasm of normal resident macrophages. In addition, these observations also demonstrate that nonactivated phagocytes may display effective microbicidal activity against certain intracellular pathogens utilizing an oxygen-dependent mechanism.
Contrasuppression. A novel immunoregulatory activity.
Authors: Gershon R K , Eardley D D , Durum S , Green D R , Shen F W , Yamauchi K , Cantor H , Murphy D B
Published: June 2004

We have described an interaction between two T cells subsets that results in interference with the expression of Ly-1-, 2+ (Ly-2) T cell-mediated suppression. We refer to this novel immunoregulatory activity as contrasuppression. The T cell responsible for the induction of contrasuppression (inducer cell) expresses the phenotype Ly-1-, 2+;I-J+;Qa-1+. This phenotype distinguishes it from the suppressor effector cells which we find to be I-J-2.3. An I-J+ soluble mediator from the contrasuppressor inducer cell acts on another cell (acceptor cell) that expresses the phenotype Ly-1+, 2+; I-J+; Qa-1+. This phenotype distinguishes it from T helper cells. Both the inducer cell (or its biologically active mediator) and its acceptor cell are required for the expression of contrasuppression. Because contrasuppressor cells can block the suppressive activity of cell-free mediators released by Ly-2 suppressor T cells, the mechanism of contrasuppression is either separated from or in addition to the inactivation of suppressor cells themselves. The potential importance of contrasuppressor activity in the regulation of suppressor T cell activity in allowing immunologic memory to be expressed and in permitting microenvironmental immune regulation is discussed.
Interaction of target cell-bound C3bi and C3d with human lymphocyte receptors. Enhancement of antibody-mediated cellular cytotoxicity.
Authors: Perlmann H , Perlmann P , Schreiber R D , Müller-Eberhard H J
Published: June 2004

The occurrence and distribution of distinct receptors for three C3 fragments on purified human blood lymphocytes were studied by rosette formation. Indicator cells were bovine, chicken, or sheep erythrocytes (E) bearing up to 100,000 molecules of human C3b (EC3b) without antibody. EC3b was converted to C3bi-bearing-E (EC3bi) with purified C3b inactivator (factor I) and beta1H (factor H), and to C3d-bearing E (EC3d) by treatment of EC3bi with trypsin. Using bovine E (Eb) as indicators, approximately 11% of the lymphocytes bound EbC3b, 6% bound EbC3bi and 2% bound EbC3d. Fractionation of the lymphocytes by adsorption to monolayers of C3-fragment-bearing Eb or by rosetting indicated that most of the cells with receptors for C3b were distinct from those having receptors for C3bi and/or C3d. Cells from two lymphoblastoid cell lines (Raji and Daudi) formed strong rosettes with EC3b, which were weak. 51Cr-labeled E was used as a target in antibody, C3-fragment-bearing E was not lysed by the lymphocytes. However, at suboptimal concentrations of IgG enhancing capacity of the fragments occurred in the order of C3bi greater than C3d greater than C3b. In addition, C3-fragment-bearing cells inhibited the lysis of antibody-coated cells not concluded that target cell bound C3 fragments enhance ADCC by improving contact between target cells and those effector cells which have C3 receptors. Cell-bound C3 effector cells. It is proposed that certain lymphocytes are capable of interacting with C3bi in addition to C3b and C3d and that C3bi and C3d have a greater regulatory effect on their cytolytic function than C3b.
Membrane distribution and adsorptive endocytosis by C3b receptors on human polymorphonuclear leukocytes.
Authors: Fearon D T , Kaneko I , Thomson G G
Published: June 2004

C3b receptors on human polymorphonuclear leukocytes (PMN) were nonrandomly distributed in small clusters on the plasma membranes of these cells when assessed by indirect immunofluorescence at 0 degree C using monospecific rabbit Fab' or F(ab')2 anti-C3b receptor and tetramethylrhodamine isothiocyanate (TRITC)-conjugated goat IgG anti-F(ab')2. When PMN were incubated with the bivalent anti-C3b receptor at 37 rather than at 0 degree C, almost no immunofluorescence was observed, which indicates that the C3b receptor-F(ab')2 complexes had been rendered inaccessible to TRITC-IgG anti-F(ab')2. Endocytosis of the anti-C3b receptor ligand was quantitated by measuring the binding 131I-IgG anti-F(ab')2 by PMN that had previously taken up 125I-F(ab')2 anti-C3b receptor at 0 and at 37 degree C, respectively. There was a constant 2: 1 molar ratio of anti-F(ab')2 to anti-C3b receptor with PMN that had been incubated with the first antibody at 0 degree C. In contrast, when increments of F(ab')2 anti-C3b receptor were taken up by the cells at 37 degree C, there was a dose-related decline in this molar ratio to a minimum of 0.2 molecules of anti-F(ab')2 anti-F(ab')2 bound per molecule of PMN-associated anti-C3b receptor. 125I-F(ab')2 anti-C3b receptor taken up by PMN at 37 degree C was also inaccessible to release by proteolytic treatment of the cells with pronase. The rate of endocytosis of 125I-F(ab')2 anti-C3b receptor was rapid as the PMN-bound antibody fragment became inaccessible to 131I-IgG anti-F(ab')2 within 10 min during incubation of the cells at 37 degree C. In contrast to these findings, 125I-Fab' anti-C3b receptor that was taken up by PMN at 37 degree C remained accessible to both 131I-IgG anti-F(ab')2 and to proteolytic release by pronase, which suggests that monovalent interaction of ligand with C3b receptors was not sufficient for induction of endocytosis. The requirement for multivalency was also demonstrated using the C3b-OR, the normal ligand for the C3b receptor. 125I-C3b-OR was specifically bound by PMN but remained on the cell receptor. 125I-C3b-OR was specifically bound by PMN but remained on the cell surface, as determined by its accessibility to pronase, unless it was cross-linked with F(ab')2 anti-C3. Although C3b receptors on PMN do not mediate internalization of adsorptive pinocytosis of soluble ligand indicates their potential for the clearance of C3b-bearing immune complexes without recruitment of other cell surface receptors.
Biogenesis of membrane-bound and secreted immunoglobulins. II. Two forms of the human alpha chain translated in vitro and processed in vivo as distinct polypeptide chains.
Authors: McCune J M , Fu S M , Blobel G , Kunkel H G
Published: June 2004

Structural differences between alpha m (ther heavy chain of membrane IgA) and alpha s (the heavy chain of secretory IgA) were investigated. Messenger RNA from the human B lymphoblastoid line 32a.1, expressing both membrane and secretory IgA, was translated in a wheat germ cell-free system, resulting in the synthesis of two primary translation products for the alpha chain, that differed in molecular weight. In vivo pulse and pulse-chase experiments demonstrated that two early biosynthetic forms of the alpha chain were subsequently modified to yield three intracellular forms. As shown by endo-beta-N-acetylglucosaminidase H (endo H) treatment, these forms represent two alpha polypeptide chains, with varying compositions of N-linked oligosaccharides. Of the two forms of the alpha chain remaining after endo H treatment, only the form with the lowest molecular weight was associated with cells after long chase periods. The possible significance of this difference from the results with mu and delta chains is discussed. These results indicate that alpha m is distinguished from an alpha s by a difference in both primary structure and intracellular processing. The functional consequences of this distinction, previously shown for the heavy chain of membrane IgM (micrometer) and heavy chain of secretory IgM (microseconds), may reflect a principle common to the secretory and membrane forms of all immunoglobulin heavy chain classes.
Expression of resistance to Friend virus-stimulated erythropoiesis in bone marrow chimeras containing Fv-2rr and Fv-2ss bone marrow.
Authors: Silver J , Teich N
Published: June 2004

Bone marrow chimeras were formed containing mixtures of DBA/2 (Fv-2ss, Hbbdd) and B10.D2 (Fv-2rr, Hbbss) bone marrow. When these mice were infected with the polycythemia-inducing strain of Friend virus, erythropoiesis was stimulated, but the proportion of B10.D2 hemoglobin fell rapidly and newly synthesized hemoglobin was essentially all of the DBA/2 type. The treatment of infected polycythemic chimeras with phenylhydrazine lowered the hematocrit and restored the synthesis of B10.D2 hemoglobin. These results imply that B10.D2 erythroid precursors are intrinsically resistant to Friend virus-stimulated erythropoiesis. The experiments also suggest that virus-stimulated erythropoiesis is not mediated by a factor or cell-cell interactions, unless such factors or interactions do not act across strain barriers.
J chain biosynthesis in pre-B cells and other possible precursor B cells.
Authors: McCune J M , Fu S M , Kunkel H G
Published: June 2004

Human cell lines that resemble precursors in the B cell lineage have been found to synthesize J chain. In vivo pulse labeling, together with in vitro translation of total cellular RNA in a wheat germ cell-free system, detected the synthesis of J chain in immunoglobulin-secreting cell lines, in a cell line with only surface IgM, as well as in the pre-B-like cell line Josh 4 and the round cell lines Josh 7 and KLM 2. The primary translation products of J chain from all of these cell lines were found to be indistinguishable from one another by serologic criteria, by relative mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, by charge as judged by alkaline-urea gel electrophoresis, and by peptide mapping. These findings suggest that the onset of J chain biosynthesis represents a relatively early event in B cell ontogeny, occurring before the development of immunoglobulin polymer-secreting cells. Its role may, consequently, be fundamental to the biosynthesis of all immunoglobulins, at different stages of B cell differentiation.
Lyt-23+ cyclophosphamide-sensitive T cells regulate the activity of an interleukin 2 inhibitor in vivo.
Authors: Hardt C , Röllinghoff M , Pfizenmaier K , Mosmann H , Wagner H
Published: June 2004

Sera of thymus-bearing normal mice contain high levels of Interleukin 2 (II-2) inhibitor, whereas sera of athymic nu/nu mice do not. Evidence is presented that cyclophosphamide-sensitive Lyt-23+ T cells induce high II-2 inhibitor activity in the recipient nu/nu mice in the course of a graft-vs.-host reaction. The II-2 inhibitor has an approximately 50,000 mol wt. Its function is neither antigen specific nor H-2 restricted. During ontogeny, its activity parallels the development of T cell reactivity, i.e., it is absent both in the amniotic fluid and in sera of unborn mice, but increases to high levels during the early postnatal phase. The II-2 inhibitor described is viewed as an example of a T cell-dependent, in vivo regulatory mechanism able to effectively counteract the nonspecific activity of the Lyt-1+ helper T cell-derived II-2. Because the II-2 inhibitor activity is rather high in vivo, II-2 activity will exist only in close proximity to its producer cell, thereby maintaining specificity during the in vivo induction of cytotoxic T lymphocytes
Genetic study of lymphoma induction by AKR mink cell focus-inducing virus in AKR x NFS crosses.
Authors: Cloyd M W , Hartley J W , Rowe W P
Published: June 2004

The mink cell focus-inducing (MCF)-247 virus, originally isolated from an AKR thymoma, is lymphomagenic in AKR mice but not in the ecotropic virus-negative NFS mouse strain. Analysis of sensitivity to lymphoma-induction by AKR-247 MCF virus in genetic hybrids between these two strains showed that F1 mice inoculated as sucklings were uniformly sensitive, whereas those inoculated as weanlings were generally resistant. In NFS backcross mice inoculated as sucklings, inheritance and expression of endogenous ecotropic virus from AKR was an essential correlate of replication of MCF virus and subsequent development of lymphoma. However, one-third of the mice expressing ecotropic virus and replicating the inoculated MCF virus did not develop lymphoma. The results suggested that an additional gene that influenced development of lymphoma may be involved, and that mice inheriting both virus-inducing loci from AKR were more susceptible than those inheriting only one. These findings indicate that the causal role of ecotropic virus infection in spontaneous thymomagenesis in AKR mice involves not only the generation of leukemogenic MCF viruses but also the establishment of permissiveness for their growth.
Retroviral gp70 immune complexes in NZB x NZW F2 mice with murine lupus nephritis.
Authors: Izui S , McConahey P J , Clark J P , Hang L M , Hara I , Dixon F J
Published: June 2004

NZB x NZW (NZB x W) F1 hybrid mice spontaneously develop a disease most prominently characterized by immune complex glomerulonephritis (GN), which seems to be associated with both antibodies to DNA and to the serum retroviral envelope glycoprotein, gp70. To evaluate the contribution of each of these autoimmune responses to the pathogenesis of the GN, we studied NZB x W F2 mice in which the two responses appeared to segregate relatively independently. Use of this model permitted analysis of possible correlations between each response and the G.N. The presence of circulating anti-gp 70-complexed gp70 correlated significantly with the development of fatal GN and one could predict the course of renal disease by computing the rising serum levels of gp70 complexed with antibodies. In contrast, the presence of free antibodies to either double-stranded or single-stranded DNA was not significantly associated with the development of fatal GN. This association of anti-gp70 antibody production with these animals' early death from GN strongly suggests that the gene(s) governing production of antibodies to serum retroviral gp70 may be one of the major genes responsible for spontaneous renal disease segregated in NZB x W F2 generations.
Type II collagen-induced arthritis in mice. I. Major histocompatibility complex (I region) linkage and antibody correlates.
Authors: Wooley P H , Luthra H S , Stuart J M , David C S
Published: June 2004

A model of arthritis was established by the injection of type II collagen into mice. Only mice bearing the H-2q haplotype were susceptible to the disease. Susceptibility was further mapped by the use of recombinant strains on the Iq locus. Type II collagen arthritis was observed in the (resistant X susceptible) F1 cross. Mice strains were designated high, intermediate, or low responders with respect to the anti-type II antibody levels measured by radioimmunoassay. Arthritis-susceptible strains were all classified as high antibody responders. The clinical and histological appearance of type II collagen arthritis in the mouse indicates that it may be a good animal model for the investigation of various immunogenetic traits in rheumatoid arthritis.
Immune responsiveness of SM/J mice. Cellular characteristics and genetic analysis of hyperresponsiveness to B cell mitogens.
Authors: Engel D , Clark E A , Held L , Kimball H , Clagett J
Published: June 2004

We tested the proliferative responses of splenocytes from a panel of inbred mouse strains to AVIS, a B cell mitogen from Actinomyces viscosus bacteria. The SM/J strain was found to exhibit severalfold higher responsiveness than any of the other strains. SM/J splenocytes were also hyperresponsive to the B cell mitogens lipopolysaccharide, dextran sulfate, and purified protein derivative of tuberculin, but responsiveness to the T cell mitogen phytohemagglutinin was normal. (B6 X SM)F1 and F1 x B6 backcross mice were tested for AVIS and lipopolysaccharide responsiveness, and it was determined that hyperresponsiveness was under polygenic, autosomal, non-H-2-linked gene control. Genetic control of response to B mitogens in SM/J mice appears to be expressed solely through the B lymphocyte because removal of T lymphocytes or macrophages did not reduce the magnitude of responsiveness in vitro. SM/J mice may provide a useful model for testing questions regarding B cell triggering, differentiation, and function, and to examine the genes involved with B cell proliferation.
New cell surface gp70 related to Friend mink cell focus-inducing virus is expressed on Friend virus-induced erythroleukemic spleen cells after elimination of ecotropic Friend virus gp70 in Rfv-3r/s mice.
Authors: Britt W J , Collins J K , Chesebro B
Published: June 2004

Spleen cells from Rfv-3r/s mice with Friend virus-induced erythroleukemia were analyzed for expression of virus-induced proteins with monoclonal antiviral antibodies and conventional antisera. Leukemic spleen cells, 30-60 d after virus inoculation, expressed decreased amounts of ecotropic Friend murine leukemia helper virus gag- and env-encoded cell surface and intracellular proteins compared with leukemic cells tested 8-10 d after virus inoculation. In contrast, the spleen focus-forming virus-induced protein, gp55, was present on both leukemia cell populations. This difference appeared to be mediated by the humoral antibody response in Rfv-3r/s mice, which could recognize only ecotropic gag and env proteins, and not gp55. A new gp70 molecule cross-reactive with a recombinant Friend mink cell focus-inducing virus was found in large quantities on late leukemic cells. This protein appeared to be derived from a recombinant virus produced during the course of Friend virus infection. The appearance of this new gp70 suggests that recombinant viruses other than spleen focus-forming virus may play a role in Friend virus-induced erythroleukemia.
Friend murine leukemia virus-induced leukemia is associated with the formation of mink cell focus-inducing viruses and is blocked in mice expressing endogenous mink cell focus-inducing xenotropic viral envelope genes.
Authors: Ruscetti S , Davis L , Feild J , Oliff A
Published: June 2004

In these studies, we have shown data that are consistent with the hypothesis that mink cell focus-inducing viruses (MCF) play an important role in the generation of an erythroproliferative disease developing after injection of certain strains of newborn mice with ecotropic Friend murine leukemia virus (F-MuLV). Resistance to this disease is correlated with the endogenous expression of an MCF/xenotropic virus-gp70-related protein that may interfere with the replication or spread of MCF viruses. These ideas are supported by the following observations: (a) after infection with F-MuLV, only 6/13 strains of mice-developed disease, and studies with crosses between susceptible and resistant strains indicated that resistance was dominant. Although F-MuLV was shown to replicate equally well in all strains tested, viruses coding for MCF-specific viral envelope proteins could be detected only in the spleens of mice from strains that were resistant to F-MuLV-induced disease and not in the spleens of mice from strains that were resistant to F-MuLV-induced disease; (b) a Friend MCF (Fr-MCF) virus isolated from the spleen of an F-MuLV-infected mouse from a susceptible strain induced the same erythroproliferative disease when injected as an appropriate pseudotype into mice from susceptible but not resistant strains of mice; and (c) resistant but not susceptible strains of mice endogenously express MCF/xenotropic virus-related envelope glycoproteins that may be responsible for resistance by blocking receptors for MCF viruses. These results not only indicate that Fr-MCF virus is a crucial intermediate in the induction of disease by F-MuLV, but also suggest that a novel gene, either an MCF/xenotropic virus-related envelope gene or a gene controlling its expression, is responsible for resistance to erythroleukemia induced by F-MuLV.
Antigen presentation to human T lymphocytes. I. Different requirements for stimulation by hapten-modified cells vs. cell sonicates.
Authors: Abramson S L , Puck J M , Rich R R
Published: June 2004

We have investigated the cellular and antigenic requirements for incubation of secondary proliferative responses by human T lymphocytes. Two distinct properties of antigen-presenting peripheral blood mononuclear cells were studied: (a) the ability for appropriate cell surface constituents to construct an immunogenic moiety, and (b) the ability to present similar antigenic determinants when they are not covalently bound. Only Ia+ hapten-modified cells were effective stimulators. In contrast, both Ia+ and Ia- cell sonicates could stimulate secondary proliferative responses, but only in the presence of an accessory cell. This accessory cell was present in Ia+ macrophage, but not in Ia+ non-T lymphocyte, preparations. In contrast, macrophages or soluble factors produced by macrophages were not required for primed T cells to undergo hapten-specific proliferation in response to hapten-modified Ia+ stimulator cells. Thus, although all Ia+ cells tested can stimulate primed cells to proliferate, not all Ia+ cells can function as accessory cells for responses to sonicates. This may reflect the unique ability of a subpopulation(s) of Ia+ cells to bind or process sonicates or soluble antigens for appropriate recognition by primed T cells.
Distribution of common acute lymphoblastic leukemia antigen in nonhematopoietic tissues.
Authors: Metzgar R S , Borowitz M J , Jones N H , Dowell B L
Published: June 2004

The common acute lymphoblastic leukemia antigen (CALLA), as defined by J-5 murine monoclonal antibodies, was detected on renal tubular and glomerular cells from fetal and adult donors by an indirect immunoperoxidase technique. CALLA could also be detected on epithelial cells of the fetal small intestine and on myoepithelial cells of adult breast but not on myoepithelial cells of the salivary gland. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of immunoprecipitated 125I-labeled membrane antigens from dissociated renal cells demonstrated that the antigen migrated as a 90,000 mol wt antigen rather than the 98,000-100,000 mol wt antigen noted on CALLA-positive tissue culture cell lines. The data suggest that the determinant defined by the J-5 monoclonal antibody is neither a lymphoid cell-specific differentiation antigen nor a leukemia-specific antigen.
Immune interferon produced to high levels by antigenic stimulation of human lymphocytes with influenza virus.
Authors: Ennis F A , Meager A
Published: June 2004

Influenza virus stimulation of human lymphocytes induced high levels of immune interferon in lymphocyte cultures. The lymphocytes of normal adults produced approximately 1,000 U/10(6) cells, which was in large part gamma interferon. The lymphocytes of individuals recently vaccinated yielded very high levels (10-50,000 U/10(6) cells) of interferon. The interferon was pH 2 labile, and was not neutralized by antisera to alpha or beta interferon. It did not bind to a monoclonal antibody to alpha interferon, and after partial purification it had characteristics identical to human gamma interferon induced by phytohemagglutinin. The highest yields were produced by treatment of stimulator cells with live virus. Stimulation by whole inactivated virus resulted in lower levels of interferon, and purified hemagglutinin did not induce interferon. The antigen responsible for stimulating the lymphocyte response and interferon induction is a cross-reactive determinant present on all human and non-human influenza viruses tested.
Monoclonal antibodies that recognize the product controlled by a gene in the I-J subregion of the mouse H-2 complex.
Authors: Kanno M , Kobayashi S , Tokuhisa T , Takei I , Shinohara N , Taniguchi M
Published: June 2004

The B cell hybridomas producing monoclonal antibodies (E10, D7, F4, H6, and D4) were established by the fusion of P3U1 or NS-1 murine myeloma cell lines and spleen cells of B10.A(5R) mice hyperimmunized with mitomycin C-treated B10.A(3R) spleen and thymus cells. Two types of monoclonal antibodies specific for the products controlled by a gene in the I-Jb subregion of the H-2 complex were characterized: one specific for the private type of I-Jb determinant, the other recognizing the cross-reactive determinant between the I-Jb and I-Jd products. By using these monoclonal reagents, the I-J-encoded product on the antigen-specific suppressor T cells was found to be expressed on their soluble suppressor factors. Furthermore, the I-Jb products were successfully detected not only on the T cell hybridoma with suppressor activity specific for keyhole limpet hemocyanin (KLH), but also on KLH-primed suppressor T cells enriched by antigen-coated petri dishes and concanavalin A-induced thymocyte blasts of C57BL/6 mice by complement-dependent cytotoxic assays and membrane fluorescence techniques.
The vascular bed as the primary target in the destruction of skin grafts by antiserum. I. Resistance of freshly placed xenografts of skin to antiserum
Authors: Jooste SV , Colvin RB , Soper WD , Winn HJ
Published: June 2004

Rat skin grafted onto immunosuppressed mice is resistant to mouse anti-rat serum during the first 7-10 d after transplantation. It gradually acquires susceptibility, reaching a peak of sensitivity at 14-16 d after grafting. The grafts remain sensitive to antiserum, though at decreasing levels for an additional 3 wk, and grafts that persist beyond that time are resistant to antiserum for as long as they survive. In the study reported here, it is shown that the initial period of resistance to antiserum is due to factors acting locally within the graft and is entirely uninfluenced by the regimen of immunosuppression or the protective dressings that are used. After administration of antiserum, deposits of the injected immunoglobulin and of endogenous C3 are found on the luminal surfaces of graft vessels, although no significant tissue damage is observed.

Rat skin that has become highly sensitive to antiserum 14-16 d after transplantation loses that sensitivity if it is regrafted to a new recipient, and then regains it 8-10 d later. Thus, the resistance of freshly grafted skin to antisera is associated with the process of healing into place, a conclusion that is supported by the observation that the intracutaneous administration of antisera to rats causes intense local inflammation and necrosis. The skin is therefore sensitive just before it is removed for grafting, but temporarily loses sensitivity thereafter. Resistance to antiserum during the first 3 or 4 d after transplantation is probably attributable to the fact that at that time grafts are vascularized poorly if at all. The state of resistance extends for several days after vascularization of the graft takes place and is then only gradually lost, a phenomenon that seems to be associated with the resistance of newly formed and regenerating blood vessels to vasoactive substances. This view is in accord with and, indeed, supports the idea that the induction of vascular injury is an essential step in antisera-mediated damage to tissue grafts.
Human cutaneous T cell lymphoma and leukemia cell lines produce and respond to T cell growth factor
Authors: Gootenberg JE , Ruscetti FW , Mier JW , Gazdar A , Gallo RC
Published: June 2004

Three cell lines of mature T cell origin derived from patients with cutaneous T cell lymphoma-leukemias (CTCL) were found to be constitutive producers of T cell growth factor (L-TCGF). These are the first reported human cell lines which constitutively produce TCGF. Biologically active TCGF could also be eluted from the surface of these cells using an acid glycine buffer under conditions that maintained cell viability, and subcellular fractionation showed that almost all the TCGF activity was associated with the plasma membrane. Over 30 other human hematopoietic cell lines derived from other disorders were unable to produce TCGF even after induction, and their acid eluates did not contain TCGF activity. L-TCGF from CTCL lines had the same biological activity as TCGF obtained from normal leukocytes (N-TCGF) in that they both supported the long-term growth of normal T cells only after the cells were previously activated by antigen or lectin. Both L-TCGF and N-TCGF increased the rate of proliferation of TCGF-independent and TCGF-dependent CTCL cell lines. The same three factor-independent cell lines that released TCGF adsorbed TCGF in a cell-concentration, time-, and temperature-dependent manner. Since the CTCL cell lines produce TCGF, adsorb TCGF, and increase their proliferative rate in response to TCGF or a related molecule, it is suggested that this endogenously produced factor plays a role in maintaining the abnormal proliferation of these cells in culture as permanently growing cell lines independent of exogenous TCGF. However, this does not mean that this is an essential aspect of neoplastic transformation. Since it is unusual to develop these cell lines in the absence of the continuous need for added TCGF, "autostimulation" may be one of the many unusual variant phenotypic properties sometimes associated with neoplastic cells that gives them a selective advantage for in vitro growth.
Analysis of the response of B cells from CBA/N-defective mice to nonspecific T cell help.
Authors: Greenstein J L , Lord E , Kappler J W , Marrack P C
Published: June 2004

We have investigated the induction of antibody responses to erythrocyte (RBC)-bound antigens in the (CBA/N x B10)F1 mouse. Male B cells, which express the CBA/N defect, were shown to be unresponsive to RBC antigens when the delivered T cell helper activity was solely nonspecific. Thus we demonstrated that defective B cells did not respond to concanavalin A supernatants or bystander helper activity, in spite of the fact that CBA/N-defective mice could produce these T cell activities. The defective B cell did not respond to RBC-bound antigen in the presence of RBC-primed T cells, although the magnitude of this response was usually twofold less than normal controls. The insensitivity of CBA/N defective B cells to nonspecific T cell helper activities seemed to involve at least the inability of RBC antigens to activate defective B cells in the absence of antigen-specific T cell help.
Murine syngeneic mixed lymphocyte response. I. Target antigens are self Ia molecules
Authors: Glimcher LH , Longo DL , Green I , Schwartz RH
Published: June 2004

A system has been described that produces a murine syngeneic mixed lymphocyte response (MLR) comparable in magnitude to an allogeneic MLR. The responder cells in these cultures exhibit the classic immunologic characteristics of both memory and specificity. Studies using radiation-induced bone marrow chimeras of F(1) {arrow} parent type indicated that, similar to many other T cell-mediated immune responses, the response of the T lymphocytes in the syngeneic MLR was major histocompatibility complex-restricted and was determined by the environment in which the T cells matured. Using responder T cells from F(1) {arrow} parent chimeras and stimulator cells from H-2 recombinant strains, it was possible to map the genes involved in the stimulation to the K and/or I regions. In addition, blocking studies with monoclonal anti-Ia antibodies suggested that in the B10.A strain the critical molecules were products of both the I-A(k) and I-E(k) subregions.

The issue of whether the syngeneic MLR is directed solely at self I-region antigens or whether the response represents proliferation to an unknown antigen in association with self I-region determinants was also addressed. Secondary syngeneic MLR were successfully performed in normal mouse serum and with stimulator cells prepared in the absence of bovine serum albumin to rule out the possibility that xenogeneic serum antigens were involved in the stimulation. The possibility that the syngeneic MLR might represent a secondary response to environmental antigens was eliminated by using germ- free mice as a source of stimulator cells and by demonstrating that spleen cells from unimmunized, fully allogeneic chimeras (B10.A {arrow} B10) could generate a normal syngeneic MLR even though such chimeras could not be primed to respond to any foreign antigens unless supplemented in vivo with a source of antigen-presenting cells syngeneic to the B10 host. The possibility that the syngeneic MLR was a primary response to a foreign antigen was considered unlikely because by using our culture conditions we could not obtain a primary antigen response or a secondary antigen response after in vitro priming to a variety of potent foreign antigens. Finally, the possibility that the syngeneic MLR represents a response to a variety of minor histocompatibility self antigens in association with self Ia molecules was eliminated by showing that the secondary responses to H-2 compatible, non-H-2 different strain (A/J vs. B10.A and C3H, or BALB/c vs. B10.D2 and DBA/2) were comparable to the secondary responses to syngeneic stimulators. Thus, we conclude that the target antigens in the syngeneic MLR are solely determinants on self Ia molecules, although the functionally equivalent possibility of a single, nonpolymorphic, minor self antigen seen in association with self Ia molecules cannot be excluded.
Malignant lymphoma with dual B and T cell markers. Analysis of the neoplastic cells with monoclonal antibodies directed against T cell subsets.
Authors: Aisenberg A C , Bloch K J , Wilkes B M
Published: June 2004

In the course of analyzing human lymphoma tissue with conventional surface marker techniques and with monoclonal antibodies directed against T cell subsets, five tumors were encountered with dual B and T cell determinants. All bore on their surface membrane IgM of kappa light chain type, complement receptors, and the Ia-like antigen. In each of the five cases, the neoplastic lymphocytes reacted with a monoclonal antibody that detects the sheep erythrocyte receptor (OKT11); all but one reacted with a monoclonal antibody for peripheral T cells (OKT3); and all but one reacted with a monoclonal antibody specific for either the inducer-helper (OKT4) or the cytotoxic-suppressor (OKT8) T cell subsets. In addition, lymphocytes from two of the five cases formed spontaneous rosettes with sheep erythrocytes (E-rosettes). These tumors with dual B and T surface characteristics were confined to human malignant lymphomas that originate from B lymphocytes of the follicle center.
Solubilization of immune precipitates by six isolated alternative pathway proteins.
Authors: Fujita T , Takata Y , Tamura N
Published: June 2004

Immune precipitates were solubilized by the alternative pathway of complement assembled from isolated proteins, i.e., C3, factor B, factor D, properdin, C3b inactivator (C3bINA), and beta 1H. The kinetic curves of solubilization in the isolated system and in EGTA-serum were virtually indistinguishable. No requirement of other factors was apparent. Deletion of C3bINA and beta 1H from the complete mixture caused total consumption of C3 in the fluid phase and resulted in neither C3 binding to the complexes nor solubilization. Thus, the presence of a regulated fluid-phase reaction is essential for efficient fixation of C3 and the consequent solubilization. In addition, properdin plays an essential role in the complement-mediated solubilization in the presence of the two regulators. A large amount of C3 was incorporated into the antigen-antibody lattice. Solubilization of immune complexes started after the binding of one C3 molecule to one antibody molecule in the complexes, and the molar ratio of C3:antibody in the solubilized complexes also is approximately 1.
Quantitative variations in the expression of H-2 antigens on murine leukemia virus-induced tumor cells can affect the H-2 restriction patterns of tumor-specific cytolytic T lymphocytes.
Authors: Plata F , Tilkin A F , Lévy J P , Lilly F
Published: June 2004

Comparative quantitative experiments were designed to study the expression of H-2Kd and H-2Dd antigens on three different leukemia cell lines induced by Gross murine leukemia virus (MuLV)in BALB/c (H-2d) mice. The H-2 restriction patterns of syngeneic cytolytic T lymphocytes (CTL) directed against Gross MuLV-induced tumors were correlated with these quantitations of H-2Kd and H-2Dd antigens, Our results obtained by quantitative absorption of monospecific antisera indicated that the three BALB/c tumor cell lines expressed different amounts of H-2Kd and H-2Dd antigens, with H-2Dd antigen showing the greatest variability in expression because it ranged from barely detectable levels to one-eighth the amount of H-2Dd antigen expressed on normal BALB/c spleen cells. The H-2 restriction patterns of Gross MuLV-specific CTL were directly affected by these quantitative modulations in the expression of H-2Kd and H-2Dd antigens, as revealed by three independent approaches: (a) inhibition of CTL activity by monospecific anti-H-2 sera in the absence of complement; (b)competitive inhibition of CTL-mediated cytotoxicity by the addition of excess tumor cells into the reaction mixture; and (c) analysis of CTL specificities using cloned CTL populations. Our results thus indicate that H-2 restriction of tumor-specific CTL activity can be directed at the target cell level by variations in the expression of H-2 antigens.