bluuebunny/crossref_metadata_2025_split huggingface dataset:
Receptor-like nature of class I HLA: endocytosis via coated pits.
Authors: Dasgupta J D , Watkins S , Slayter H , Yunis E J 
Published: December 2022

Abstract
The present investigations show that class I HLA are internalized by macrophage/monocyte type cells. Anti-class I antibody-binding assays show that about 30% of class I Ag present on cell surface are endocytosed within 1 h. Electronmicroscopic investigations reveal that, like other well established receptor molecules, internalization of HLA is mediated by coated pits and coated vesicles. The endocytosed Ag are transferred from endosomes to trans-Golgi reticulum and trans-Golgi cisternae, suggesting recycling of these Ag back to the cell surface. In the presence of phorbol ester tetradecanoyl phorbol acetate, there is a modest increase in the rate of internalization. These results are consistent with the hypothesis that class I Ag on monocytes/macrophages behave like receptor molecules. Malignant transformation of monocytic cells apparently causes the loss of this property of class I Ag.
Role of lymphokine-activated killer cells as mediators of veto and natural suppression.
Authors: Azuma E , Kaplan J 
Published: December 2022

Abstract
Fresh bone marrow cells have veto activity but little if any NK activity. By contrast, lymphokine-activated bone marrow cells have potent natural suppressor as well as veto activity, and also have cytolytic activity characteristic of lymphokine-activated killer cells. Veto activity of fresh bone marrow cells is eliminated by 9 Gy irradiation and by depletion of cells expressing Qa-2, but is unaffected by removal of cells expressing Thy-1, Qa-5, Ly-5, or asialo GM1. By contrast, the veto and NS activities of lymphokine-activated bone marrow cells are both abrogated by C lysis depletion of cells expressing Qa-2, Qa-5, Thy-1, asialo GM1, NK1, and Ly-11, but are unaffected by depletion of cells expressing Ly-2. Bone marrow cells depleted of Qa2+ cells fail to generate veto or natural suppressor activity when cultured in Con A-conditioned medium, unlike bone marrow cells depleted of mature NK1.1+ NK cells. Cloned NK cell line F8 is able to mediate both natural suppression and veto. These findings indicate that bone marrow veto and natural suppression are not mediated by T or NK cells present de novo in the bone marrow, but are dependent on proliferating cells that phenotypically resemble pre-NK cells. The progeny of these cells have the phenotype and functional activity of lymphokine-activated killer cells, and are capable of directly mediating both veto and natural suppression.
Booster irradiation to the spleen following total body irradiation. A new immunosuppressive approach for allogeneic bone marrow transplantation.
Authors: Lapidot T , Singer T S , Salomon O , Terenzi A , Schwartz E , Reisner Y 
Published: December 2022

Abstract
Graft rejection presents a major obstacle for transplantation of T cell-depleted bone marrow in HLA-mismatched patients. In a primate model, after conditioning exactly as for leukemia patients, it was shown that over 99% of the residual host clonable T cells are concentrated in the spleen on day 5 after completion of cytoreduction. We have now corroborated these findings in a mouse model. After 9-Gy total body irradiation (TBI), the total number of Thy-1.2+ cells in the spleen reaches a peak between days 3 and 4 after TBI. The T cell population is composed of both L3T4 (helper) and Lyt-2 (suppressor) T cells, the former being the major subpopulation. Specific booster irradiation to the spleen (5 Gy twice) on days 2 and 4 after TBI greatly enhances production of donor-type chimera after transplantation of T cell-depleted allogeneic bone marrow. Similar enhancement can be achieved by splenectomy on day 3 or 4 after TBI but not if splenectomy is performed 1 day before TBI or 1 day after TBI, strengthening the hypothesis that, after lethal TBI in mice, the remaining host T cells migrate from the periphery to the spleen. These results suggest that a delayed booster irradiation to the spleen may be beneficial as an additional immunosuppressive agent in the conditioning of leukemia patients, in order to reduce the incidence of bone marrow allograft rejection.
Adoptive T cell transfer of autoimmune nonobese diabetic mouse diabetes does not require recruitment of host B lymphocytes.
Authors: Bendelac A , Boitard C , Bedossa P , Bazin H , Bach J F , Carnaud C 
Published: December 2022

Abstract
The autoimmune nonobese diabetic mouse, a model of human juvenile type I diabetes mellitus, exhibits features of both B and T cell autoreactivity against insulin-producing cells. Using the neonatal cell transfer model of the disease, which we have described previously, we have shown that B cell suppression of newborn recipients by anti-mu treatment did not affect the transfer of diabetes by means of T cells. B cell-depleted, purified T cells from diabetic adults were injected into newborns treated with either IR-52, a control rat myeloma protein, or LOMM.9, a rat anti-mouse mu-chain mAb. Both groups developed diabetes over a similar time scale. Although the pancreases in both groups showed massive infiltration by T lymphocytes, B lymphocytes, presumably recruited in the host, were present in the IR-52-treated group, whereas they were absent in the LOMM.9-treated group. Anti-mu-treated diabetic animals showed substantial B cell suppression in vivo and in vitro when compared with IR-52-treated controls. These results suggest that B cell autoreactivity is a secondary phenomenon that is unimportant during the effector phase of diabetes in nonobese diabetic mice.
The antigen-binding T cell factor PCl-F sensitizes mast cells for in vitro release of serotonin. Comparison with monoclonal IgE antibody.
Authors: Meade R , Van Lovern H , Parmentier H , Iverson G M , Askenase P W 
Published: December 2022

Abstract
Picryl chloride factor (PC1-F) is an antigen (TNP hapten)-binding T cell factor that initiates PC1 contact sensitivity (CS). PC1-F initiates PC1 CS by mediating an early 2-h skin swelling reaction that is due to local release of the vasoactive amine serotonin (5-HT) by mast cells, and perhaps other 5-HT-containing cells. Experiments were conducted to determine if PC1-F could sensitize normal mast cells in vitro for subsequent release of 3H-5-HT that had been taken up previously. It was found that PC1-F could sensitize mast cells, inasmuch as incubation with PC1-F, followed by washing, resulted in the ability to release 5-HT by challenge with Ag (TNP-bovine serum albumin), or by an anti-factor mAb called 14-30. As with release induced by anti-TNP IgE mAb PC1-F-induced release required phosphatidyl serine. Mast cell sensitization and activation for 5-HT release by PC1-F was not due to contamination of PC1-F with IgE antibody, because IgE (and not PC1-F) was sensitive to reduction and alkylation. Also, affinity columns linked with 14-30 or anti-IgE showed that the mast cell sensitizing and activating property of PC1-F was clearly separate from that of IgE. PC1-F-induced release was not IgE dependent, because mast cells that were acid-stripped and largely depleted of surface IgE, could then be sensitized by PC1-F. In vivo experiments demonstrated that local challenge with 14-30 antibody induced a 2-h ear swelling reaction in actively contact sensitized mice, or adoptive recipients of sensitized cells, and in normal mice that received PC1-F i.v. These findings suggest that in vitro sensitization of mast cells with PC1-F, and subsequent in vitro release of 5-HT induced by challenge with 14-30 antibodies, correlates with the initiation of PC1 CS in vivo. Therefore, in the initiation of CS by PC1-F, mast cells can be one source of 5-HT, to cause the early, vasoactive phase of CS.
Intrinsic resistance to viral infection. Mouse macrophage restriction of herpes simplex virus replication.
Authors: Sarmiento M 
Published: December 2022

Abstract
Macrophages isolated from mice resistant to acute (lethal) infection with a neurovirulent isolate of HSV-1 express intrinsic resistance to viral infection in vitro. Bone marrow (BM), spleen (S), peritoneal (P), and thioglycolate-stimulated peritoneal (Pthio) macrophages isolated from resistant C57BL/6 Cr (B6) mice consistently restrict HSV-1 macromolecular synthesis earlier in the viral replicative cycle than do macrophages isolated from the same tissue sources from more susceptible DBA/2Cr (D2) mice. B6-BM (BM macrophages from B6 mice) restrict HSV macromolecular synthesis at least at two points in the replicative cycle: 1) before the onset of alpha-protein synthesis and 2) between the onset of gamma 1 protein and DNA synthesis. D2-BM macrophages restrict HSV replication at about the time of DNA synthesis. B6-P macrophages restrict HSV replication shortly after gamma 1 protein synthesis, and D2-P macrophages inhibit the virus slightly later, but before DNA synthesis. B6-S macrophages restrict HSV replication at about the time of DNA synthesis, and D2-S macrophages inhibit replication after the onset of gamma 2 protein synthesis. Pthio macrophages are more permissive to HSV infection than BM, P, or S macrophages: restrictions in viral replication occur at the time of DNA synthesis in B6-Pthio macrophages, and after the onset of gamma 2 protein synthesis in D2-Pthio cells. These studies demonstrate that isolated macrophages from inbred mouse strains express intrinsic resistance to HSV infection that correlates with in vivo resistance to acute (lethal) infection. Intrinsic resistance to HSV-1 infection is due to restriction of viral macromolecular synthesis. HSV replication is inhibited in macrophages at multiple points in the viral growth cycle, depending on the tissue from which the cells are isolated.
Tryptophan degradation in transplanted tumor cells undergoing rejection.
Authors: Yoshida R , Park S W , Yasui H , Takikawa O 
Published: December 2022

Abstract
The depletion of an essential amino acid, tryptophan, caused by indoleamine 2,3-dioxygenase induction in vitro, has been shown to be due to a mechanism that is used in self-defense against inhaled microorganisms and tumor growth. In this communication, we report the results of measuring dioxygenase activity in the peritoneal exudate cells and tumor cytotoxicity at the transplantation loci after in vivo transplantation of tumor cells into the peritoneal cavity of syngeneic or allogeneic strains of mice. The enzyme was induced only when the tumor cells were being rejected from allogeneic animals and no change was observed when the cells continued to grow in syngeneic animals. Furthermore, when the syngeneic tumor cells in a diffusion chamber were i.p. transplanted simultaneously with i.p. injection of allogeneic tumor cells, the enzyme was induced not only in allografted tumor cells but also in the syngeneic tumor cells. Under these conditions, the tumor cells in the diffusion chamber ceased to grow and 50% of the cells were rejected. To determine the type of cells containing the induced enzyme, the peritoneal exudate cells (tumor cells and host cells--mostly small lymphocytes) were separated into six fractions by sedimentation under gravity and by differential centrifugation. Approximately 80% of total enzyme activity was localized in a tumor-rich fraction (98.9% purity), whereas only 0.2% of the activity was found in a lymphocyte-rich fraction (99.5% purity). The localization of indoleamine 2,3-dioxygenase in the tumor cells was confirmed by complement-dependent lysis with specific antibodies against tumor and host cells.
IFN-treated neuroblastoma cell lines remain resistant to T cell-mediated allo-killing, and susceptible to non-MHC-restricted cytotoxicity.
Authors: Main E K , Monos D S , Lampson L A 
Published: December 2022

Abstract
Neuroblastoma cell lines can have very low MHC Ag expression. The cell lines are insensitive to allo-killing by primed CTL, but are sensitive to non-MHC-restricted cytotoxicity. IFN-gamma increased class I expression, but the cells remained insensitive to CTL. Susceptibility to nonrestricted effectors was preserved. Class I+ glioma cell lines behaved similarly. The CTL resistance was localized to the recognition phase. Neuroblastoma lines did not form conjugates with primed T cells, but were lysed if they were coupled to the effectors via lectins. The levels of class I expression, and resistance to CTL, were constant over a range of IFN doses. HLA-A,B,C structure and distribution were studied more intensively on one cell line, CHP-100. HLA-A2 and -A3 were present on greater than or equal to 99% of the cells, in a unimodal distribution. After IFN treatment, the levels were similar to B cell controls. In two-dimensional gel electrophoresis, the molecules co-migrated with those of B cell controls. The defect may thus be in accessory proteins that are necessary for T cell recognition or binding, rather than in the structure or distribution of the HLA-A,B,C proteins.
CD4 positive Leu-8 negative helper-inducer T cells predominate in the human intestinal lamina propria.
Authors: Kanof M E , Strober W , Fiocchi C , Zeitz M , James S P 
Published: December 2022

Abstract
The regulatory function of peripheral blood CD4 T cells correlates with the presence or absence of the membrane glycoprotein recognized by anti-Leu-8 antibody; CD4,Leu8- T cells help Ig synthesis and CD4,Leu-8+ T cells suppress Ig synthesis. In contrast to CD4 T cells from the peripheral blood and organized gut-associated lymphoid tissues, intestinal lamina propria CD4 T cells were found to have diminished expression of the Leu-8 Ag. Therefore, studies were performed to determine whether the decreased expression of the Leu-8 Ag on lamina propria CD4 T cells correlates with a difference in the ability of peripheral blood and lamina propria CD4 T cells to regulate PWM-stimulated Ig synthesis. At high T cell to non-T cell ratios, the helper function of lamina propria CD4 T cells was significantly higher than that of peripheral blood CD4 T cells. When CD4 T cells were incubated with anti-Leu-8 antibody, the suppressor function of peripheral blood CD4 T cells was increased, but lamina propria CD4 T cells did not suppress Ig synthesis. No difference was found between the helper function of CD4,Leu-8- T cells and the suppressor function of CD4, Leu-8+ T cells isolated from either the peripheral blood or the lamina propria. Thus, the difference in the regulatory function of CD4 T cells from the peripheral blood and the lamina propria is due to the quantitative difference in CD4,Leu-8+ T cells in these sites. Consequently, the intestinal lamina propria is a site enriched in CD4,Leu-8- T cells which predominantly mediate help for Ig synthesis.
Evidence against expression of an endogenous murine leukemia virus causing cellular resistance to lysis by activated macrophages.
Authors: Gooding L R , Taylor J R , Laster S M , Wehrly K , Chesebro B , Brickell P M , Latchmann D S , Rigby P W 
Published: December 2022

Abstract
In previous studies we observed that resistance of murine SV40-transformed fibroblast cell lines to cytolysis by activated macrophages was frequently associated with cellular expression of the gp70 of an endogenous ecotropic murine leukemia virus (MuLV). The work described here was initiated to test directly for a causative relationship between MuLV expression and resistance to lysis by macrophages. Northern blot analysis revealed that macrophage-resistant cells contain full length retroviral RNA. A panel of mAb which distinguish among host-range classes of MuLV detected only a non-recombinant ecotropic gp70 in these cells. The ecotropic MuLV from two independently derived macrophage resistant cells were isolated by limiting dilution cloning on Mus dunii fibroblasts. These viruses were then used to infect macrophage-sensitive cell lines and the resultant MuLV-positive cells tested for sensitivity to macrophage cytolysis. The MuLV-infected lines remained highly sensitive to macrophage lysis despite their high levels of cell surface gp70 and release of infectious MuLV. Thus, although we cannot rule out the possibility that MuLV or a product thereof is necessary for development of macrophage resistance in transformed cells, expression of MuLV per se is not sufficient to create the resistant phenotype.
Differential L chain expression in the antibody responses to phosphorylcholine of adult bone marrow or peritoneum-derived B lymphocytes.
Authors: Cazenave P A , Martinez C , Coutinho A 
Published: December 2022

Abstract
Lethal irradiation of adult BALB/c mice followed by reconstitution with autologous bone marrow results in loss of T15 Id and IdX expression in the responses to phosphorylcholine (PC) and alpha(1-3)-dextran, respectively. T15 Id, but not IdX expression can be reconstituted with low numbers of syngeneic, T cell-depleted peritoneal resident cells. All three groups of mice produce comparable titers of specific anti-PC and anti-dextran antibodies. The inability of adult bone marrow-reconstituted BALB/c mice to produce T15 Id+ antibodies is not due to differential VH-gene expression in bone marrow or peritoneum-derived B cells. Thus, the levels of T15 VH in total serum Ig and in anti-PC antibodies are similar in all groups of mice. Furthermore, IEF patterns of T15 VH-associated L chains directly demonstrate differential Vk repertoire expression in bone marrow and peritoneum-derived B cells.
Mouse fetal thymus lobes cultured in IL-2 generate CD3+, TCR-gamma delta-expressing CD4-/CD8+ and CD4-/CD8- cells.
Authors: Ceredig R , Medveczky J , Skulimowski A 
Published: December 2022

Abstract
Whole, undisrupted, 14-day fetal mouse thymus lobes were liquid-cultured in medium supplemented with 10 U/ml rIL-2. The cells that emerged from these fetal thymus lobes grew in an IL-2-dependent manner and showed non-MHC-restricted cytolytic activity. By two-color flow microfluorimetric analysis they could be subdivided into CD4-/CD8+ and CD4-/CD8- subpopulations, both of which contained CD3+ cells. Northern analysis of total cellular RNA revealed full-length transcripts of gamma- and delta-message, predominantly the truncated (1.0 kb) beta- and no detectable alpha-message. Taken together, these results show that by culturing 14-day fetal thymus lobes in IL-2, in the absence of deliberate mitogen stimulation, CD3+, TcR-gamma delta-expressing CD4-/CD8+ and CD4-/CD8- T cells are obtained. Such cells may represent the precursors of similar cells found outside the thymus in adult mice.
Expression of lymphocyte adhesion receptors for high endothelium in primates. Anatomic partitioning and linkage to activation.
Authors: Willerford D M , Hoffman P A , Gallatin W M 
Published: December 2022

Abstract
Glycoproteins of 90 to 95 kD Mr are involved in adhesion to high endothelium and migration into secondary lymphoid tissues in several species. Recent evidence indicates that in primates, one type of these molecules may be subsumed under the CD44 grouping of lymphocyte differentiation Ag. Flow cytometric analysis of circulating macaque lymphocytes for expression of these structures revealed a prominent bimodal distribution, defining two subpopulations with a 5- to 10-fold difference in immunofluorescence staining intensity. Studies of lymphocytes from different anatomic compartments revealed marked differences in the relative numbers of these two phenotypes: splenic and peripheral blood lymphocytes were mostly CD44hi, whereas thoracic duct lymphocytes, which have recently exited lymph nodes and Peyer's patches, were predominantly CD44lo, suggesting that these subsets may have different migratory behavior in vivo. Activated lymphocytes, as defined by light scatter measurements, expression of IL-2-R, and CD45R levels, were all CD44hi. Simultaneous three parameter flow cytometric determination of CD44 and CD45R expression, and cell-cycle analysis with 7-amino actinomycin D further demonstrated that intrinsically cycling cells were contained in the CD44hi, CD45R+ subset. After stimulation of CD44lo lymphocytes in vitro with cross-linked anti-CD3 antibodies and PMA, CD44 expression markedly increased. These data indicate that CD44 up-regulation is an early event in T lymphocyte activation in vivo, and support the hypothesis that patterns of lymphocyte traffic are regulated in concert with cell activation, possibly by differential expression of CD44.
Quantitative analyses of immune network components.
Authors: Lacy M J , Dombrink-Kurtzman M A , Voss E W 
Published: December 2022

Abstract
Polyclonal immune network antibodies were quantitated and characterized in a syngeneic BALB/c murine system. Immunizations of BALB/c antifluorescein mAb 9-40 conjugated to keyhole limpet hemocyanin, produced anti-Id (anti-9-40, 39 to 190 micrograms/ml) as well as anti-fluorescein (anti-Fl, 12 to 109 micrograms/ml). Separately, immunizations of polyclonal anti-9-40, developed significant anti-Fl serum levels in the secondary (2 degrees) response (50 to 270 micrograms/ml), which decreased in the 3 degrees response (50 to 180 micrograms/ml) and thereafter, although levels of 9-40 idiotypically related antibodies increased. Polyclonal 2 degrees anti-anti-9-40 exhibited variant anti-Fl active sites, was antigenically more cross-reactive than polyclonal 2 degrees anti-Fl, but did not exhibit affinity maturation for fluorescein relative to 1 degrees anti-anti-9-40. In addition, the 9-40 idiotype constituted a small (less than 1.0%) percent of the 2 degrees and 3 degrees anti-Fl (ab1) immune response. When viewed within the context of an antigenic system that possesses widely diverse idiotypy, continued introduction of polyclonal anti-Id appears eventually to: 1) induce polyclonal ab3 with quantitative expression of idiotypically related antibodies in preference to ab3 of ancestral (9-40) antigenic specificity, 2) relative to ab1, induce a 100-fold increase in the level of ab3 antibodies that have both ancestral idiotype and ancestral antigen reactivity, and 3) induce polyclonal ab3 antibodies with a measurably wider range of antigenic reactivities than those of polyclonal ab1. These quantitative data may reflect the natural state of an immune network in a diverse antigenic response.
Unique intermolecular bactericidal epitope involving the homosialopolysaccharide capsule on the cell surface of group B Neisseria meningitidis and Escherichia coli K1.
Authors: Jennings H J , Gamian A , Michon F , Ashton F E 
Published: December 2022

Abstract
The N-propionylated group B meningococcal polysaccharide mimics a unique bactericidal epitope on the surface of group B meningococci and Escherichia coli K1. This was confirmed when both the above organisms were able to absorb the bactericidal antibodies from a mouse-anti-N-propionylated group B meningococcal polysaccharide-tetanus toxoid conjugate serum. By using affinity columns it was possible to divide the conjugate antiserum into three distinct populations of both group B polysaccharide cross-reactive and non-cross-reactive antibodies, one of which contained most of the bactericidal activity. The cross-reactive (IgG1) antibodies were absorbed by an affinity column in which the group B polysaccharide was linked to the solid support by a long spacer arm, thereby isolating a population of non-cross-reactive (IgG1) antibodies. Surprisingly the above column also retained another population of non-cross-reactive (IgG2a) and (IgG2b) antibodies which contained most of the bactericidal activity. These latter antibodies were not absorbed by a similar group B polysaccharide-affinity column in which a short spacer arm was employed. Thus the above experiments not only effected a separation of highly bactericidal antibodies but also provided evidence that the long spacer arm is functional in the binding of the bactericidal antibodies to the affinity column. This indicates that the bactericidal epitope is mimicked by the group B polysaccharide in the presence of the long spacer arm, which supports the hypothesis that the epitope is polysaccharide-associated and is probably intermolecular in nature.