bluuebunny/crossref_metadata_2025_split huggingface dataset:
Idiotype vaccines against human T cell leukemia. II. Generation and characterization of a monoclonal idiotype cascade (Ab1, Ab2, and Ab3).
Authors: Bhattacharya-Chatterjee M , Chatterjee S K , Vasile S , Seon B K , Kohler H 
Published: December 2022

Abstract
Previously, we had generated anti-Id mAb (Ab2) binding to a hybridoma SN2 (Ab1), which recognizes a glycoprotein, gp37, expressed by human leukemic T cells. To characterize these anti-idiotopes further, they were used to immunize mice and rabbits. Several murine anti-anti-Idiotype mAb (Ab3), mostly of IgM-k isotype, were obtained. mAb3 and sera from rabbits immunized with Ab2 contained antibodies that bind to gp37 Ag and leukemic MOLT-4 and JM cells. Also, mAb3 and immune sera from rabbits competed with Ab1 for binding to MOLT-4 cells. They inhibited the binding of iodinated Ab1 to Ab2 indicating that Ab3 in mice and rabbits shares idiotopes with Ab1 (SN2). Furthermore, both the murine mAb3 and rabbit polyclonal Ab3 immunoprecipitated the same gp37 Ag as SN2 (Ab1). The production of Ag-specific Ab3 (Ab1') in mice and rabbits in absence of any exposure to gp37 indicates that these Ab2 may indeed carry the internal image of the gp37 Ag. Such anti-idiotopes (Ab2 beta) may be useful as Ag substitute for the induction of therapeutic immunity in T cell leukemia patients.
IL-1 as a co-factor for lymphokine-secreting CD8+ murine T cells.
Authors: Mizuochi T , McKean D J , Singer A 
Published: December 2022

Abstract
Immunologically important among the known biologic activities of IL-1 is its ability to function as a co-factor for responses mediated by lymphokine secreting CD4+ Th cells. In contrast to its known effects in CD4+ T cell responses, IL-1 is not known to play a role in CD8+ T cell responses. In the present study, we have assessed the ability of murine recombinant IL-1 to function as a co-factor for stimulating CD8+ T cells to secrete lymphokines such as IL-2. We found that, in conjunction with either Ag or mitogen, IL-1 is able to stimulate lymphokine-secreting CD8+ T cells. Furthermore, we found that, as a consequence of its stimulation of lymphokine-secreting CD8+ T cells, IL-1 is able to reconstitute MHC class I allospecific cytolytic T lymphocyte responses by cell populations depleted of both accessory cells and CD4+ T cells. These results demonstrate that the biologic activity of IL-1 is not restricted to CD4+ cell responses, and suggests that IL-1 can function as a co-factor for the stimulation of lymphokine-secreting Th cells regardless of their CD4/CD8 phenotype. If IL1 acts directly on lymphokine-secreting T cells or on the APC with which they interact is not yet certain.
DNA rearrangements affecting both variable and constant regions of Ig H chain genes in MPC11 mouse myeloma variants.
Authors: Gilmore G L , Bard J A , Birshtein B K 
Published: December 2022

Abstract
We have examined the mechanisms that account for short Ig H chain production in two variants of the mouse myeloma cell line MPC11 (IgG2b, kappa) by mRNA sequencing and restriction enzyme mapping. One variant, F5.5, has a thymidine residue inserted into the (CH3) domain, of the Ig H chain, resulting in premature termination and translation of a gamma 2b H chain of 50,000 m.w. A second variant, E5.7A12, contains gamma 2a-derived sequences that extend from near the 3' end of the CH2 domain to the intervening sequence between the CH2 and CH3 domains, consistent with a microrecombination event (defined as either a double cross-over or gene conversion event). In this variant, the 5' end of the CH3 domain has been deleted, but the remainder of the gamma 2b(CH3) domain is present, resulting in the translation of a gamma 2b-gamma 2a-gamma 2b H chain of 52,000 m.w. Additional rearrangements affecting sequences in or adjacent to the variable region accompany H chain constant region alterations in these cell lines and subclones of these cell lines. In F5.5, novel sequences have recombined within one of two duplicated copies of the VH gene. In a sister clone of E5.7A12 that has ceased H chain production (E5.7A14), new sequences have recombined within 300 bp 5' of the enhancer element. Both F5.5 and E5.7A12, like their immediate unstable precursor cells, fail to assemble H-H dimers, halting the Ig assembly process at the heavy-light stage, and do not secrete H chains. We speculate that defects in H chain assembly and secretion, as exemplified by the parents of these variants (i.e., intermediates of these secondary variants), reactivate the Ig gene rearrangement machinery and result in the formation of these putatively equally unstable secondary variants.
Analysis of T hybridomas prepared from a T cell clone with three specificities. Recognition of self + X and allo-H-2 determinants segregates from recognition of Mlsa determinants.
Authors: Webb S R , Okamoto A , Sprent J 
Published: December 2022

Abstract
To see k information on T cell recognition of Mlsa determinants, hybridomas were prepared from a well-characterized F23.2+ (V beta 8.2+) T cell clone specific for three different ligands, i.e., 1) Mlsa determinants, 2) fowl gamma-globulin (F gamma G) plus self-H-2 (H-2d), and 3) allo-H-2, e.g., H-2p, determinants. Fusion of the clone to the BW5147 thymoma line produced a triple-reactive T hybridoma which generated two types of spontaneous variants. One type of variant (type I) lost Mlsa reactivity but retained reactivity to both F gamma G/H-2d and allo-H-2p. These variants, which were generated at high frequency, stained strongly with a mAb, A1.57, with idiotypic specificity for the TCR molecules of the parental clone. The second type of variant (type II) reacted to Mlsa determinants but showed no reactivity to F gamma G/H-2d or to allo-H-2p. These variants failed to express the A1.57 idiotypic determinants of the parent clone, but were F23.2+ (V beta 8.2+); nonequilibrium pH gradient electrophoresis analysis suggested that these hybrids expressed a mixed TCR heterodimer composed of the parental clone beta-chain and the BW5147 alpha-chain. Three aspects of the data are very difficult to accommodate with the view that Mlsa, F gamma G, and allo-H-2 determinants are all recognized via a common TCR molecule: 1) the independent (and frequent) segregation of Mlsa reactivity from F gamma G/H-2d and allo-H-2p reactivity, 2) the retention of Mlsa reactivity by the type II variants despite loss of the parental clone alpha-chain, and 3) the loss of Mlsa reactivity by the type I variants despite high expression of the A1.57+ TcR molecules derived from the parental clone. The data support a model in which Mlsa determinants are recognized by a separate T cell structure, which we envisage as a monomorphic accessory molecule unrelated to the TCR. Since the type II hybridoma variants invariably retained quantitatively normal TcR expression, the triggering phase of anti-Mlsa responses appears to be TCR dependent. The model we favor is that anti-Mlsa/Mlsa interaction increases TCR binding with Ia epitopes to above the threshold required for cell triggering. A key feature of this model is that Mlsa and Ia determinants are recognized as separate structures rather than as a complex.
Idiotypic vaccination as a treatment for a B cell lymphoma.
Authors: George A J , Folkard S G , Hamblin T J , Stevenson F K 
Published: December 2022

Abstract
To develop a model for the active immunotherapy of human B cell malignancy we vaccinated tumor-bearing animals with a well defined tumor associated Ag, the idiotypic Ig. The tumor used was the mouse B cell lymphoma BCL1, a highly malignant tumor in which transfer of a single tumor cell to a syngeneic mouse is capable of causing disease and eventual death. Varying doses (10(2) to 10(4] of BCL1 cells were given to mice on day 0 of the experiment, and treatment by active immunization was initiated on day 3. Immunization with purified, tumor-derived, idiotypic IgM (BCL1 IgM) coupled to keyhole limpet hemacyanin (KLH) was highly effective in treating mice challenged with 10(2) or 10(3) BCL1 cells, but less effective in mice that had received 10(4) tumor cells. Immunization with unconjugated BCL1 IgM showed no signficant therapeutic benefit. Coupling of the IgM to KLH led to higher levels of anti-idiotypic antibody after immunization; however, the higher levels were probably not responsible for the control of the malignancy as there was no correlation in healthy immunized animals between the levels of anti-idiotypic antibody, measured immediately before tumor challenge, and survival. This lack of correlation is due to the emergence of variant tumors in such protected mice. A more significant factor in the therapeutic advantage of KLH conjugation could be that immunization with BCL1 IgM-KLH led to an earlier induction of the anti-idiotypic response than immunization with BCL1 IgM and, as the BCL1, lymphoma divides rapidly, the speed of induction of the immune response may be important in outstripping tumor cell growth. Mice with BCL1 tumour showed some evidence of immunosuppression as indicated by a reduced ability to mount an immune response against KLH. Although it is not possible to model spontaneous human lymphoma accurately, the generation of a functional anti-idiotypic response capable o eliminating a malignant animal lymphoma in situ opens up the possibility of a limited trial of active immunotherapy in selected human patients.
Release of tumor necrosis factor-alpha from macrophages. Enhancement and suppression are dose-dependently regulated by prostaglandin E2 and cyclic nucleotides.
Authors: Renz H , Gong J H , Schmidt A , Nain M , Gemsa D 
Published: December 2022

Abstract
PGE2 has previously been shown to suppress various leukocyte functions. In this study, we examined whether PGE2 would affect release of TNF-alpha from rat resident peritoneal macrophages. Two different, dose-dependent effects were observed: low PGE2 concentrations (0.1 to 10 ng/ml) stimulated, whereas higher concentrations (greater than 10 ng/ml) suppressed TNF-alpha release. PGE2-stimulated TNF-alpha production was dependent on de novo protein synthesis and was associated with an intracellular rise of cGMP. The importance of cGMP as an intracellular messenger for PGE2 was confirmed by the following evidence: (1) low PGE2 concentrations preferentially increased cGMP and not cAMP and (2) cGMP, either exogenously added or endogenously generated by sodium nitroprusside, were efficient stimulators of TNF-alpha production. In contrast, agents increasing intracellular cAMP concentrations such as PGE1, higher PGE2 doses, isoproterenol, and theophylline, all suppressed TNF-alpha synthesis. Only resident, but not casein-elicited or Corynebacterium parvum-activated macrophages, were stimulated by low PGE2 concentrations to increase TNF-alpha production. In tumor cytotoxicity assays, PGE2-activated macrophages were active only against TNF-alpha-sensitive target cells. These findings demonstrate that TNF-alpha synthesis in macrophages is up-regulated by cGMP and down-regulated by cAMP, which indicates that cyclic nucleotides act as intracellular messengers for extracellular signals of macrophage activation.
Generation and functional characterization of T cell lines and clones specific for Schistosoma japonicum egg antigen in humans.
Authors: Ohta N , Edahiro T , Tohgi N , Ishii A , Minai M , Hosaka Y 
Published: December 2022

Abstract
T cell lines specific for Schistosoma japonicum egg Ag were established in vitro from patients with chronic schistosomiasis japonica, and investigated their possible immunopathologic roles by testing lymphokines production and in vitro granuloma formation assay. All lines tested had surface phenotypes of CD3+ CD4+ CD8-, and showed S. japonicum soluble egg Ag (SEA)-specific proliferation requiring HLA-DR-restricted Ag presentation. Of these fractions of SEA separated by gel filtration, Fraction II (m.w. 7,000 to 18,000) and III (m.w. 7,000) induced strong proliferation of T cell lines, whereas fraction I (m.w. 18,000+) failed to induce detectable proliferation to any T cell lines tested. One of the T cell lines was cloned by micromanipulation: two of eight clones responded only to fraction II, and six to both fractions II and III. We observed that four of eight clones tested produced IL-2 in response to SEA, and three of them were able to transfer S. japonicum egg-specific granulomatous hypersensitivity in vitro to an HLA haplo-identical individual without previous schistosome infection. These immunopathologic functions of T cell clones seemed to be activated by at least two distinct epitopes of SEA. Our present observations suggest that at least two distinct CD4+ human T cells, both of which recognize epitopes expressed on SEA molecules of less than 18 kDa, might have critical roles in granulomatous hypersensitivity to eggs of S. japonicum in humans.
A monoclonal antibody reacting with distinct adhesion molecules defines a transition in the functional state of the receptor CD11b/CD18 (Mac-1).
Authors: Altieri D C , Edgington T S 
Published: December 2022

Abstract
CD11b/CD18 (Mac-1) is a member of the leukocyte integrin family, a group of receptors that have been implicated in various effector functions and cellular collaboration in the immune response. It has been shown previously that CD11b/CD18 on cells of monocyte and myeloid lineage appears to undergo rapid activation and acquire new functional receptor specificities after exposure to selected agonists such as adenosine diphosphate (ADP). We now show that ADP induces a reconformation of the CD11b/CD18 receptor with exposure of new epitopes characteristics of this activated state. By direct binding studies, flow cytometry, and immunoprecipitation experiments, it has been found that the mAb 7E3 reacts with CD11b/CD18 only after ADP-stimulation of the cell suspension. The activated state of CD11b/CD18 induced by ADP and recognized by 7E3 can also be recapitulated by agonists inducing transients in cytosolic Ca2+ such as the chemoattractant FMLP. Moreover, this process of receptor activation does not involve quantitative mobilization of the subcellular storage pool of CD11b/CD18 to the plasma membrane. Because 7E3 also recognizes a qualitative, ADP-mediated activated state of the platelet adhesion receptor GP IIb/IIIa, it is suggested that transients in cytosolic Ca2+ might represent early secondary events for a general pathway of rapid activation of integrin receptors and, as such, represent important signals for cellular interactions in the immune response.
Fine mapping of an H-2Kk restricted cytotoxic T lymphocyte epitope in SV40 T antigen by using in-frame deletion mutants and a synthetic peptide.
Authors: Rawle F C , O'Connell K A , Geib R W , Roberts B , Gooding L R 
Published: December 2022

Abstract
The CTL response to SV40 in C3H/HeJ mice is directed against the tumor (T) Ag and is H-2Kk restricted. CTL specific for both the amino terminus (residues 1-271) and the carboxyl terminus (residues 512-708) of the T Ag molecule have been detected, and we have previously cloned CTL of both specificities. In this paper we show that the panel of 10 CTL clones specific for the C-terminal region includes clones specific for three different epitopes, termed C1, C2, and C3. Epitopes C1 and C2 are conserved in the T Ag of the related papova viruses BK and SA12, and only epitopes C2 and C3 are present on SV40 transformed targets bearing the Kk mutant Kkml. Epitopes C1 and C2 were mapped to residues 563-576 by using in-frame deletion mutants of SV40 T antigen, and all clones specific for these two epitopes can lyse Kk bearing target cells in the presence of a synthetic peptide comprising residues 559-576. Kk and Kkml differ at residue 152, which is located in the Ag-binding pocket. Because epitopes C1 and C2 can be formed by the same antigenic peptide, but epitope C1 is not present on SV40 transformed Kkml cells, epitopes C1 and C2 must differ in the contribution made by residue 152 of the MHC class I molecule. These data show that CTL epitopes on transformed cells can be made up of Ag fragments, and strengthen the idea that this is a general phenomenon for both class I and class II restricted T cell epitopes.
Ig lambda-producing B cells do not show feedback inhibition of gene rearrangement.
Authors: Gollahon K A , Hagman J , Brinster R L , Storb U 
Published: December 2022

Abstract
In order to study the regulation of expression of Ig lambda genes we have analyzed lambda-producing hybridomas derived from transgenic mice which harbor a functionally rearranged kappa transgene. We also analyzed lambda-producing hybridomas from nontransgenic mice. Surprisingly, all but one of the transgenic lambda-hybridomas co-produce kappa L chains. Also, in contrast to transgenic kappa-hybridomas, most lambda-hybridomas have rearranged endogenous kappa genes despite the presence of transgenic kappa-chains and endogenous H chains. Analysis of spleen cells and hybridomas from nontransgenic mice shows that about 20% of lambda-producing B cells in the spleen co-produce kappa, and a similar proportion of lambda-hybridomas from normal spleens produce both kappa- and lambda-chains. The data argue strongly against the strictly sequential expression of kappa and lambda genes. We present a new model for the regulation of kappa and lambda gene expression, whose key feature is the distinction between a kappa cell lineage in which Ig gene rearrangement is susceptible to feedback by a complete antibody molecule at the pre-B cell stage, and a kappa lambda B cell lineage which does not show feedback inhibition during B cell development.
Comparison of the cytotoxic potency of T101 Fab, F(ab')2 and whole IgG immunotoxins.
Authors: Derocq J M , Casellas P , Laurent G , Ravel S , Vidal H , Jansen F 
Published: December 2022

Abstract
The in vitro killing of the human CEM cell line was studied by using ricin A-chain immunotoxins constructed with either the whole IgG or the Fab and F(ab')2 fragments of the same T101 (anti-CD5) antibody. In the presence of ammonium chloride as an activator, the "whole" immunotoxin as well as the "fragment" immunotoxins did not show any significant difference in the cell killing efficacy. In contrast, without the activator, the efficacy of the T101 immunotoxin was greatly improved when fragments were used. Indeed, at a saturating dose, a cytoreduction of three orders of magnitude was obtained with the fragment immunotoxins vs less than one order of magnitude for the whole immunotoxin, as assessed in a clonogenic assay. This enhancing effect was related to better cell killing kinetics, because with a similar amount of A-chain molecules bound per cell, T101 fragment immunotoxins achieved a twofold faster protein synthesis inactivation rate than the corresponding whole IgG immunotoxin. No significant difference in activity was shown between monovalent (Fab) and divalent (F(ab')2) forms of fragment immunotoxins. The observation that T101 fragment immunotoxins were more potent than intact immunotoxins was extended to another fragment immunotoxin constructed with an antibody (F111.98) directed against a different epitope of the CD5 Ag. In another model (anti-CD22 1G11 antibody on Raji cells), the fragment immunotoxin did not show any superiority over the IgG immunotoxin which was by itself very potent, strongly suggesting an Ag-dependent phenomenon.
Protein kinase C modulates actin conformation in human T lymphocytes.
Authors: Phatak P D , Packman C H , Lichtman M A 
Published: December 2022

Abstract
We studied the effect of activators and inhibitors of protein kinase C on actin conformation in human blood lymphocytes by flow cytometry and gel electrophoresis. PMA, 1-oleyl-2-acetyl-glycerol, and mezerein, activators of protein kinase C, caused an increase in lymphocyte F-actin within 2 to 5 min. After stimulation with PMA, lymphocytes formed pseudopods containing an increased concentration of F-actin and had an increase of actin in the Triton-insoluble cytoskeletal fraction. Sphingosine and H-7, inhibitors of protein kinase C activation, inhibited the increase in F-actin induced by PMA. The increase in F-actin in response to PMA was striking in Th and Ts lymphocytes (2- to 3-fold increase), but B lymphocytes had only a slight increase (1.15-fold). Thus, activation of protein kinase C modulates actin conformation specifically in T lymphocytes.
Complete nucleotide sequence of the chromosomal gene for human IL-4 and its expression.
Authors: Arai N , Nomura D , Villaret D , DeWaal Malefijt R , Seiki M , Yoshida M , Minoshima S , Fukuyama R , Maekawa M , Kudoh J 
Published: December 2022

Abstract
We have isolated a chromosomal DNA segment of the human IL-4 gene based on homology with a human IL-4 cDNA sequence and determined its complete nucleotide sequence. The human IL-4 gene, which occurs as a single copy in the haploid genome, is mapped on chromosome 5. It is composed of four exons and three introns and is approximately 10 kilobase pairs in size. 5'-Flanking regions of human and mouse IL-4 genes share about 85% homology extending more than 500 base pairs upstream of a "TATA" like sequence. Several patches of sequences are found in the 5'-flanking region of the human IL-4 gene which are homologous to sequence in the 5'-flanking regions of the IL-2, IL-3, IL-5, and granulocyte-macrophage (GM)-CSF genes. The IL-4 gene is inducible after treatment of human T cell clone by phorbol-12-myristate-13-acetate (TPA) and calcium ionophore A23187. The 2.3-kb 5'-flanking region of the human IL-4 gene transiently transfected into Jurkat human T cell leukemia cells is activated efficiently in response to TPA and A23187 stimulation and, although less efficiently, by human T cell leukemia virus type I-encoded p40x or BPV-encoded E2 protein. Combination of TPA/A23187 and p40x or E2 protein further augmented the level of expression.
An in situ study of B-lymphocytopoiesis in rat bone marrow. Topographical arrangement of terminal deoxynucleotidyl transferase-positive cells and pre-B cells.
Authors: Hermans M H , Hartsuiker H , Opstelten D 
Published: December 2022

Abstract
To understand bone marrow (BM) as a site of B-lymphocytopoiesis, insight into the topographical arrangement of developing B cells and their relationships to the microenvironment in vivo is required. To study the spatial distribution of B lymphocyte progenitors defined by intracellular markers (cytoplasmic mu H chain and nuclear terminal deoxynucleotidyl transferase (TdT], we developed a technique to cut frozen femurs of rat, yielding cross-sections with intact subendosteal and central marrow. By using (double) immunofluorescence staining techniques we located pre-B and TdT+ cells, and IgM+ B cells in those sections. Of the B cells present in BM, one-third was accumulated in the lumen of blood sinuses. The rest were in the BM parenchyma, as were virtually all pre-B and TdT+ cells. The subendosteal area was twice as rich in pre-B and TdT+ cells as the central area, and within the subendosteal area a profound positive gradient toward the bone was evident. B cells showed an equal distribution over the center and the periphery of the BM. The distribution patterns of B lineage cells in the BM parenchyma were analyzed and shown in part to deviate from random distribution. Additional study of clonal development and microenvironmental factors in hematopoiesis will have to clarify the underlying mechanisms for the observed distribution patterns of B cell precursors in BM.