bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nucleotide sequence of a DRw10 beta chain cDNA clone. Identity of the third D region with that of the DRw53 allele of the beta 2 locus and as the probable site encoding a polymorphic MHC class II epitope.
Authors: Merryman P , Gregersen P K , Lee S , Silver J , Nuñez-Roldan A , Crapper R , Winchester R 
Published: December 2022

Abstract
The nucleotide and inferred amino acid sequence of a DRw10 beta chain was obtained from cDNA clones isolated from a DR1, DRw10 heterozygous cell line. The sequence of this beta chain gene was distinctive, differing from those of all other defined DR types. The DRw10 beta chain gene was shown by transfection experiments to encode a polymorphic epitope recognized by mAb 109d6 that is also encoded by the DRw53 beta 2 chain gene. Comparison of the nucleotide sequence of both genes revealed that their third D regions (amino acids 67 to 73) were identical. This suggested first that the 109d6 epitope could be encoded by residues of this region, and second, that a putative gene conversion event transferred this sequence along with the information encoding the 109d6 epitope from a donor gene such as DRw53 beta 2. The sequence of the DRw10 beta chain gene was observed to be identical to that of clone pII beta 4 derived from the non-DR3 haplotype in the Raji cell line, which was also demonstrated to express the determinant recognized by antibody 109d6, suggesting that the typing of this cell line is HLA-DR3/DRw10. No evidence was found for the existence of a DR beta 2 chain gene product encoded by the DRw10 haplotype. The DRw10 haplotype was of particular interest because it was present along with a DR1 haplotype in the propositus who had rheumatoid arthritis, and was shared by the DR4-positive son of the propositus, who also had rheumatoid arthritis. This raised the possibility that the DRw10 haplotype, and most probably one or more specific conformations encoded by the DR beta chain, are involved in the definition of the disease susceptibility phenotype.
A C terminus cysteine of diphtheria toxin B chain involved in immunotoxin cell penetration and cytotoxicity.
Authors: Dell'Arciprete L , Colombatti M , Rappuoli R , Tridente G 
Published: December 2022

Abstract
The role of diphtheria toxin (DT) B-chain subdomains in DT cytotoxicity and immunotoxin mechanism of action has been investigated. OKT3 (mAb to the CD3 surface Ag of human T lymphocytes) was conjugated to DT or the DT mutant CRM 1001, which has a cys----tyr substitution at position 471 of the B chain. OKT3-CRM 1001 immunotoxin was about 1400-fold less cytotoxic for CD3 Jurkat cells than OKT3-DT and had a 12-fold slower kinetics of protein synthesis inactivation, CRM 1001 killed DT-sensitive Vero cells at a 5000-fold higher concentration than DT. Its cell surface-binding activity was comparable to DT. Based on kinetics of cell inactivation, toxicity determination at low extracellular pH and Triton X-114 distribution, it was concluded that CRM 1001 is defective in at least one crucial step of toxin penetration and is unable to cross cell membranes as efficiently as DT. The substituted cysteine appears to be important for DT translocating functions. Data on the function of DT B-chain subdomains are relevant for the study of whole toxin conjugates and their mechanism of action.
Phorbol myristate acetate inhibits increases in membrane fluidity induced by anti-IgM in B cells.
Authors: Mizuguchi J , Utsunomiya N , Nakanishi M , Arata Y 
Published: December 2022

Abstract
Anti-IgM or anti-IgD stimulates B cells to induce increases in inositol phospholipid metabolism and intracellular free calcium concentration [( Ca2+]i). Anti-IgM also causes increases in membrane fluidity that occur more promptly than those in [Ca2+]i in resting B cells as well as BAL17 B lymphoma cells. However, other B cell activators such as LPS or PMA did not induce the membrane fluidity changes. Furthermore, sodium fluoride, which is considered to be an activator of the guanine nucleotide-binding protein, caused increases in membrane fluidity as well as increased [Ca2+]i or inositol phospholipid metabolism. Anti-IgM- or sodium fluoride-induced increases in membrane fluidity were inhibited by 20-min pretreatment of cells with PMA, but not by 24-h pretreatment. These results indicate that membrane fluidity changes are closely associated with increased [Ca2+]i after cross-linkage of membrane Ig and are regulated by protein kinase C in B cells.
The development of helper T cell precursors in mouse thymus.
Authors: Marrack P , Kushnir E , Born W , McDuffie M , Kappler J 
Published: December 2022

Abstract
We have examined the appearance in mouse ontogeny of thymocyte precursors for Ag-specific, MHC-restricted Th. These cells are first detectable at day 18 of fetal life, about 1 day after alpha/beta, TCR-positive cells begin to appear. These early Th precursors are not dependent on the thymus for priming with Ag and MHC, and are L3T4+, Lyt-2-. Thus, these cells already have the phenotype of mature Th. In neonatal F1 animals expressing both IAk and IAb, the appearance of Th precursors restricted by either IAk or IAb is specifically inhibited by treatment of the mice with anti-IAk or anti-IAb antibodies, respectively. These results indicate that cells of mature T cell phenotype and function can arise fairly rapidly from immature, receptor-bearing precursors, once these appear. Moreover the results are in line with those previously obtained in chimeric animal experiments which suggested that specific interaction of TCR on thymocytes with class II alleles in the thymus is required for the subsequent appearance of T cells restricted by those class II alleles.
IFN-mediated induction of MHC antigen expression on human keratinocytes and its influence on in vitro alloimmune responses.
Authors: Niederwieser D , Auböck J , Troppmair J , Herold M , Schuler G , Boeck G , Lotz J , Fritsch P , Huber C 
Published: December 2022

Abstract
The MHC Ag expression on the surface of keratinocytes is altered after treatment with IFN. IFN-gamma induces, as expected, a strong increase in class I MHC Ag expression as well as de novo expression of class II MHC Ag, whereas IFN-alpha 2 only slightly increases class I MHC Ag and does not induce keratinocytes to express class II MHC Ag. We used untreated and IFN-pretreated keratinocytes as stimulators and also as targets to study whether IFN-induced MHC Ag changes would alter the immunogenicity of keratinocytes in alloimmune responses. It was found that class II MHC Ag-carrying keratinocytes were unable to induce the proliferation of resting lymphocytes, but did stimulate T blasts. Untreated keratinocytes were virtually resistant to the lysis by classical CTL but became susceptible after exposure to IFN-gamma, but not IFN-alpha 2 at physiologic doses. These data demonstrate mechanisms by which the release of IFN-gamma might contribute to the development of disease such as the graft vs host disease.
Mechanism of defective natural killer cell activity in patients with AIDS is associated with defective distribution of tubulin.
Authors: Sirianni M C , Soddu S , Malorni W , Arancia G , Aiuti F , Soddus S 
Published: December 2022

Abstract
Previous studies have demonstrated the importance of some cytoskeleton components in killing mechanisms. In fact, a microtubule and microfilament (MF) rearrangement in the lytic sequence of CTL and NK cells has been observed. In particular, MF seem to be related to the binding phase, because MF inhibitors suppress the binding of NK cells to the target, whereas microtubule inhibitors suppress only the killing phase. In this paper, the distribution of two cytoskeleton components, actin and alpha- and beta-tubulin, has been studied in PBL from AIDS patients, who maintain the capacity to bind to the target cell line K562 but are not able to kill it. PBL were labeled with mAb to these two cytoskeleton components, and then indirect immunofluorescence was used to visualize their distribution in the conjugates. A normal polarization of actin in the effector PBL was found, whereas no tubulin rearrangement was evident in the effector and target cells. On the contrary, in conjugates of PBL or large granular lymphocytes from normal donors and K562, a polarization of actin in the effector cell and a polarization of tubulin both in the effector and in the target cells, at the site of the attachment, was evident. These data suggest that a deficiency of tubulin rearrangement may underlie the inability of the NK cells from AIDS patients to kill their target.
Characterization of a suppressor cell line which downgrades experimental autoimmune uveoretinitis in the rat.
Authors: Caspi R R , Kuwabara T , Nussenblatt R B 
Published: December 2022

Abstract
A Ts lymphocyte line was isolated from spleens of rats primed with the retinal soluble Ag (SAg) in the anterior chamber of the eye. This line could inhibit in vitro SAg-driven proliferation of uveitogenic Th lymphocytes, in a radioresistant, Ag-independent manner. Adoptively transferred Ts line cells were found to downgrade experimental autoimmune uveoretinitis in actively immunized syngeneic recipients. The initial surface phenotype (OX8+) of the Ts line was unstable in vitro, however, the cells expressed suppressor function irrespective of phenotype. The mechanism of suppression did not appear to involve consumption of IL-2 or direct cytolysis of uveitogenic Th lymphocytes, but rather the production of a soluble suppressor factor. These findings may suggest an in vivo role for suppressor lymphocytes, capable of inhibiting primed Th cells, in the regulation of experimental autoimmune uveoretinitis.
Development of a human monoclonal antibody from a Graves' disease patient that identifies a novel thyroid membrane antigen.
Authors: Baker J R , Saunders N B , Kaulfersch W , Burman K D 
Published: December 2022

Abstract
To investigate the interaction between antibodies and the thyroid gland in Graves' disease, PBL were harvested from seven Graves' disease patients and transformed into lymphoblasts by the addition of EBV in the presence of cyclosporine A. These lymphoblasts were cloned by limiting dilution and then assayed for binding activity to human thyroglobulin, thyroid-stimulating hormone, thyroid microsome, and thyroid as well as guinea pig fat cell membranes. Four patients' cells produced antibody that bound to at least one of the Ag; a single clone from one patient that bound equally well to both thyroid and guinea pig fat cell membranes (but not to other thyroid Ag) was selected for further evaluation. Fusion of these cells with SHM-D33 heteromyeloma cells yielded three cell lines that produced genetically identical mAb. Immunostaining of human thyrocytes with this mAb demonstrated an Ag present on both nuclear and cell membranes. This Ag was identified as an 18,000 m.w. protein band on Western blots of both human thyroid and guinea pig fat cell membranes. The mAb was also able to alter thyrocyte physiology as the short term incubation of this mAb with FRTL-5 cells in vitro inhibited thyroid-stimulating hormone-mediated production of cAMP. Thus, this mAb and the Ag it identifies may be relevant to Graves' disease.
Role of L3T4+ and Lyt-2+ donor cells in graft-versus-host immune deficiency induced across a class I, class II, or whole H-2 difference.
Authors: Moser M , Sharrow S O , Shearer G M 
Published: December 2022

Abstract
The i.v. injection of parental T cells into F1 hybrid mice can result in a graft-vs-host (GVH)-induced immune deficiency that is Ag nonspecific and of long duration. The effect of the GVH reaction (GVHR) on the host's immune system depends on the class of F1 MHC Ag recognized by the donor cells. To determine the role of different subsets of donor-derived T cells in the induction of GVHR, donor spleen cells were negatively selected by anti-T cell mAb and C, and the cells were injected into F1 mice that differed from the donor by both class I and II MHC Ag or by class I or class II MHC only. The induction of GVHR across class I + II differences was found to require both L3T4+ and Lyt-2+ parental cells. Induction of GVHR across a class II difference required only L3T4+ parental T cells in the combination tested [B6-into-(B6 x bm12)F1]. In contrast, B6 Lyt-2+ cells were sufficient to induce GVHR across a class I difference in (B6 x bm1)F1 recipients. In addition, a direct correlation was observed between the cell types required for GVH induction and the parental T cell phenotypes detected in the spleens of the GVH mice. The number of parental cells detected in the unirradiated F1 hosts was dependent upon the H-2 differences involved in the GVHR. Induction of a class I + class II GVHR resulted in abrogation of both TNP-self and allogeneic CTL responses. In contrast, induction of a class II GVHR resulted in only a selective loss of TNP-self but not of allogeneic CTL function. Unexpectedly, the induction of a class I GVHR also resulted in the selective loss of the TNP-self CTL response. Thus, these class I and class II examples of GVH both result in the selective abrogation of L3T4+ Th cell function. The data are discussed in terms of respective roles of killer cells and/or suppressor cells in the induction of host immune deficiency by a GVHR, and of the selective deficiency in host Th cell function induced by different classes of GVHR.
Lysis of cells infected with HIV-1 by human lymphocytes targeted with monoclonal antibody heteroconjugates.
Authors: Zarling J M , Moran P A , Grosmaire L S , McClure J , Shriver K , Ledbetter J A 
Published: December 2022

Abstract
The present study was undertaken to determine whether human PBL can be specifically focused to lyse cells infected with HIV-1 by mAb heteroconjugates that can bridge target and effector cells. A mAb directed against the central portion of HIV-1 glycoprotein gp110 was chemically cross-linked to a mAb directed against the CD3/TCR complex or to a mAb directed against the CD16 Fc gamma-R expressed on large granular lymphocytes (LGL). HIV-1-infected cells, but not uninfected cells, were found to be lysed to a greater extent by PBL in the presence of the gp110 X CD3 or the gp110 X CD16 antibody heteroconjugate than in the presence of the single antibodies or a mixture of the mAb comprising the heteroconjugates. Pretreatment of PBL with anti-CD3 or IL-2 augments their ability to lyse HIV-1-infected cells in the presence of the heteroconjugates. Lysis by anti-CD3-activated PBL in the presence of the gp110 X CD3 heteroconjugate was found to be mediated by CD8+-enriched T cells, whereas lysis by IL-2-treated PBL in the presence of the gp110 X CD16 heteroconjugate is mediated by PBL enriched for CD16+ cells, which are primarily LGL. Furthermore, PBL from asymptomatic, HIV-1-infected seropositive donors were found to be functional in lysing HIV-1-infected cells in the presence of the antibody heteroconjugates. Such antibody heteroconjugates, which can target T cells or LGL to lyse HIV-1-infected cells, may be of prophylactic or therapeutic value in HIV-1-infected individuals.
Regulation of colony-stimulating factor 1-dependent macrophage precursor proliferation by type beta transforming growth factor.
Authors: Strassmann G , Cole M D , Newman W 
Published: December 2022

Abstract
Transforming growth factor (TGF) type beta, a potent growth modulator, has recently been shown to inhibit the proliferation and function of several types of immune cells. This report investigates the effect of human platelet purified TGF-beta on CSF-1-induced proliferation in liquid cultures. We used two cell types to study TGF-beta effects, bone marrow precursors and a c-myc partially transformed CSF-1-dependent macrophage cell line designated BMM-8. We found that CSF-1-dependent proliferation of both cell types was strongly inhibited by TGF-beta in a dose-dependent manner. Approximately 1.6 and 8 pM TGF-beta inhibited 50% of CSF-1 proliferation of the bone marrow precursors and BMM-8, respectively. Inhibition appeared to be reversible, as bone marrow and BMM-8 cells proliferated in response to CSF-1 after preincubation of the cells in TGF-beta. Interestingly, inhibition of hematopoietic cells was observed only after a lag period of 24 to 48 h after onset of cultures. TGF-beta inhibition was partially diminished when increasing amounts of CSF-1 were added to the cultures. TGF-beta inhibition did not involve secondary inhibitory factors such as IFN or PG, both of which have been previously shown to suppress CSF responsiveness. Finally, flow cytometric analysis of the cell cycle indicated that within 48 h, TGF-beta-treated BMM-8 cells were prevented from entering S phase. These results suggest that TGF-beta may play an important role in the negative regulation of macrophage production.
Phosphorylation of a 15- to 17-kDa protein correlated with lytic function in cytotoxic T lymphocytes.
Authors: Filiaggi M C , McCulley D E , Russell J H 
Published: December 2022

Abstract
CTL are activated to lyse their targets through the interaction of the CTL-R and the appropriate Ag on the surface of the target cell. Experiments with tumor-promoting phorbol esters have suggested that the activation and translocation of protein kinase C (PKC) to the CTL membrane may be important in the activation process. We have studied the functional role of PKC in lytic signal transduction by correlating the phosphorylation of a set of CTL membrane proteins bound by the lectin Con A with lytic function in CTL clones. The data obtained indicate that the phosphorylation of a 15- to 17-kDa polypeptide in this subset is associated with the translocation of PKC to the membrane and the stimulation of lytic function. This suggests that the 15- to 17-kDa protein may be a physiologically relevant substrate for PKC translocated to the membrane as a result of Ag-specific perturbation of the CTL-R.
The toxicity of rat large granular lymphocyte tumor cells and their cytoplasmic granules for rodent and African trypanosomes.
Authors: Albright J W , Munger W E , Henkart P A , Albright J F 
Published: December 2022

Abstract
To explain previous findings that rodent and African trypanosomes are relatively insusceptible to the actions of NK cells, their sensitivity to the cytotoxicity of rat LGL tumor cells and isolated cytolysin-containing granules was studied. LGL tumor cells displayed modest spontaneous killing of rodent trypanosomes but were considerably more effective in the antibody-dependent cell-mediated cytotoxicity mode in the presence of specific antibody. The trypanosomes were quite resistant to lysis by the cytolysin-containing granules, compared with other types of cells. The slow inefficient lysis that occurred in the presence of divalent cations involved granule concentrations thousands of times greater than was required for lysis of SRBC. Rodent trypanosomes were significantly more susceptible to lysis when divested of their surface glycoprotein coats. In the absence (or near absence) of divalent cations, a substance (or substances) present in the granules rapidly destroyed intact and nude trypanosomes; this activity probably was not associated with cytolysin. The rate and efficiency with which the divalent cation-independent substance destroyed three species of trypanosomes indicate that this material deserves further study with an eye to its potential use as a therapeutic agent.
Trans-acting regulatory factors for T cell antigen receptor alpha- and gamma-chain gene expression.
Authors: Maeda K , Nakashima M , Komori S , Watanabe T 
Published: December 2022

Abstract
BALB/c mouse thymoma-derived T cell line, CAK4.4 (Thy-1+, L3T4-, Lyt-2-), produced a large amount of TCR-gamma mRNA, a trace amount of TCR-beta mRNA but no detectable level of TCR-alpha mRNA. Another BALB/c mouse thymoma-derived T cell line, CAK1.3 (Thy-1+, L3T4+, Lyt-2+), synthesized a high level of TCR-alpha as well as TCR-beta mRNA but did not produce any amount of TCR-gamma mRNA. HAT-sensitive clones were established from the two T cell lines. Azaguanine-resistant, HPRT- CAK4.4 cells and bromodeoxyuridine-resistant, TK- CAK1.3 cells were fused by electrofusion method and the resultant hybrids were analyzed for expression of TCR genes as well as the changes of their cell surface phenotypes. Transcription of TCR-gamma gene was completely suppressed in all hybrids tested, although Southern blot analysis showed that the hybrids maintained TCR-gamma chain genes derived from both parental cells. TCR-alpha gene transcription occurred normally in one hybrid. In two other hybrids, TCR-alpha gene transcription was strongly suppressed. Treatment of the hybrid cells with 12-O-tetradecanoyl phorbol-13-acetate reversed the suppression of TCR-alpha gene transcription, but TCR-gamma gene transcription was not recovered by the same treatment. However, transcription level of TCR-beta gene was not changed in all hybrids. Our results suggested that the different trans-acting regulatory mechanisms control the transcription levels of TCR-alpha and TCR-gamma genes and that such a transcriptional control may play a crucial role in the determination of orderly appearance of TCR-gamma and TCR-alpha gene products during T cell ontogeny in the thymus.
Specific enhancement of the therapeutic effect of anti-idiotype antibodies on a murine B cell lymphoma by IL-2.
Authors: Berinstein N , Starnes C O , Levy R 
Published: December 2022

Abstract
We have previously reported on the augmentation of monoclonal anti-Id antibodies by IL-2 in the therapy of a murine B cell lymphoma. The mechanism of this augmentation was through the expansion by IL-2 of effector cells mediating antibody-dependent cellular cytotoxicity. In this paper we explore the power of IL-2 to enhance anti-Id therapy on larger tumor burdens and at sites distant from the site of injection. The combination treatment was able to induce regression of established 1-cm s.c. tumors associated with microscopic metastatic tumor in lungs, liver, and spleen. Further studies into the mechanism of activity showed that IL-2 was unable to augment in vivo or in vitro tumor lysis by F(ab')2 fragments, thus emphasizing the importance of Fc interactions with antibody-dependent cellular cytotoxicity effector cells. FcR-bearing NK cells were increased in the peritoneum of IL-2-treated mice. The augmented therapeutic effect by the combination treatment was specific for tumor cells expressing the target Id, and non-specific cytotoxicity on Id-negative variants was not seen.
Anti-CD2 monoclonal antibodies and calcium ionophore A23187 modulate lytic activity in CD4+ and CD8+ alloreactive clones.
Authors: Inverardi L , Geller R L , Gleason J T , Gromo G 
Published: December 2022

Abstract
Alloreactive cytolytic clones can be modified in terms of their lytic specificity by several agents. We have evaluated the effects of anti-CD2 and anti-CD3 mAb and the calcium ionophore A23187 on CD4+ and CD8+ allospecific cytolytic clones. All these agents can modify the specificity of clones although the range of targets lysed depends on the agent used and subtype of the clone. Inhibition studies suggest that surface structures that are involved in non-specific cell-cell interaction processes play a role in this non-MHC-restricted cytolysis.
Capacity of purified unprimed Lyt-2+ cells to reject Ia- H-2-different tumor cells in the Winn assay.
Authors: Sprent J , Schaefer M 
Published: December 2022

Abstract
To examine which cells participate in primary anti-H-2 responses to Ia- tumors in vivo, irradiated mice were injected intracutaneously with small doses of tumor cells mixed with purified populations of host-type lymphoid cells. Studies with three different Ia- H-2-different tumors showed that purified unprimed Lyt-2+ cells were highly efficient at suppressing tumor growth. Lyt-2+ cells were appreciably more effective at suppressing tumor growth than unseparated T cells, and no protection was seen with injection of L3T4+ cells (except in the late states of tumor growth). It is suggested that class I alloantigens on the tumors are directly immunogenic for Lyt-2+ cells. Without need for help from L3T4+ cells, the responding Lyt-2+ cells rapidly differentiate into cytotoxic cells and destroy the tumor cells before macroscopic tumors can arise.