bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence that lymphokine-activated killer cells and natural killer cells are distinct based on an analysis of congenitally immunodeficient mice.
Authors: Andriole G L , Mulé J J , Hansen C T , Linehan W M , Rosenberg S A 
Published: December 2022

Abstract
The in vitro incubation of lymphoid cells in RIL 2 results in the generation of LAK cells that are broadly lytic to autologous, syngeneic, and allogeneic fresh tumor cells, but which do not lyse fresh, normal cells. Strains of mice with congenital immunodeficiencies were tested both for the presence of NK cells and for their capacity to generate LAK cells after in vitro incubation with IL 2. Splenocytes obtained from two immunodeficient mouse strains (NIH-Beige-Nude and NIH-Beige-Nude-XID) failed to generate LAK cells, but displayed significant activity. Splenocytes from another immunodeficient mouse strain (NIH-Beige-XID) generated LAK cells but did not display NK cell activity. This dissociation of activation of LAK cells from NK cells among the immunodeficient strains indicates that the LAK and NK cell lytic systems are distinct.
Active transformation of tolerogenic to immunogenic signals in T and B cells by 8-bromoguanosine.
Authors: Scheuer W V , Goodman M G , Parks D E , Weigle W O 
Published: December 2022

Abstract
The injection of deaggregated human gamma-globulin (DHGG) into A/J mice results in the establishment of a state of unresponsiveness to subsequent challenge with immunogenic aggregated human gamma-globulin (AHGG). Administration of the B cell activator 8-bromoguanosine (8BrGuo) 3 hr after administration of DHGG converts the tolerogen to an immunogen and results in an antibody response of even greater magnitude than the primary response elicited by AHGG alone. Adoptive transfer studies with separated populations of T and B cells demonstrated that although transformation of the tolerogenic signal to an immunogenic signal involves effects of 8BrGuo on both T cells and B cells, the major effect appears to be activation of antigen-specific T cells that would otherwise become tolerant. Modulation of T cell tolerance could conceivably be mediated either by direct or indirect mechanisms. Interestingly, optimal responsiveness of B cells from animals treated with DHGG and 8BrGuo is not a T cell-independent event, but requires antigen-reactive T cells. 8BrGuo is not able to override unresponsiveness when given 10 to 20 days after tolerance induction, at a time point when both T and B lymphocytes are tolerant. However, when given at day 60, when T cells (but not B cells) remain tolerant to this antigen, the nucleoside is able to terminate the tolerant state prematurely, possibly by providing an alternate T helper-like signal directly to B cells or by recruiting nonspecific functional T helper cells.
Suppressor T cells, distinct from "veto cells," are induced by alloantigen priming and mediate transferable suppression of cytotoxic T lymphocyte responses in vivo.
Authors: Owens T , Crispe I N 
Published: December 2022

Abstract
Primary and secondary cytotoxic T lymphocyte responses to minor alloantigens can be suppressed by priming host mice with a high dose (10(8) cells) of alloantigenic donor spleen cells (SC). Such suppression is antigen specific and transferable into secondary hosts with T cells. One interpretation of this is that antigen-specific host suppressor T cells (Ts) are activated. Alternatively, donor Lyt-2+ T cells, introduced in the priming inoculum, may inactivate host CTL precursors (CTLp) that recognize the priming (donor) alloantigens. Donor cells that act in this way are termed veto T cells. The experiments described here exclude veto T cell participation in transferable alloantigen-specific suppression, and demonstrate the operation of an alloantigen-specific host-derived T suppressor (Ts) cell. The origin of the Ts has been studied directly by using Thy-1-disparate BALB/c mice. The cell responsible for the transfer of suppression of a secondary CTL response to B10 minors was of the host Thy-1 allotype, and so originated in the host spleen and was not introduced in the priming inoculum. Secondly, antigen-specific Ts generated in CBA female mice against B10 minors could act on CTL responses to an unequivocally non-cross-reactive-third party antigen (H-Y), provided the two antigens were expressed on the same cell membrane. Such third-party suppression is incompatible with the operation of veto T cells. Depletion of Thy-1.2+ or Lyt-2+ cells from the suppression-inducing donor SC inoculum did not abrogate suppression induction in BALB/c mice; instead, suppression was enhanced. The demonstration of veto cell activity in similarly primed mice by other groups of investigators indicates that both types of suppression may operate. However, our results show that only antigen-specific Ts can mediate the transferable suppression of CTL responses to alloantigens.
Genetics of insulin-specific helper and suppressor T cells in nonresponder mice.
Authors: Jensen P E , Kapp J A 
Published: December 2022

Abstract
The role of insulin-specific helper and suppressor T cells in the H-2-linked genetic control of antibody responses to heterologous insulins was examined in vitro. These data demonstrate that pork insulin stimulates both primed helper T cells and dominant suppressor T cells in all nonresponder strains tested. Thus, the nonresponder phenotype is attributed to the activation of specific suppressor T cells rather than to an absence of helper T cell activity. Examination of the antigenic cross-reactivity patterns of pork insulin-primed helper and suppressor T cells in various strains demonstrates that fine specificity of the helper T cells differs from that of the suppressor T cells and that the patterns of antigenic cross-reactivity of these subpopulations are controlled by the H-2 gene complex. Furthermore, in a given strain of mice variants of insulin that stimulate helper T cells that cross-react with mouse insulin also stimulate dominant suppressor T cells that cross-react with mouse insulin. Such variants of insulin are perceived as nonimmunogenic. These observations raise the possibility that nonresponsiveness that is controlled by H-2 linked genes results from the activation of regulatory mechanisms involved in maintaining self-tolerance.
Mechanisms of suppressed cell-mediated immunity and impaired antigen-induced interleukin 2 production in granuloma-bearing mice.
Authors: Kobayashi K , Allred C , Yoshida T 
Published: December 2022

Abstract
Pulmonary granulomas were induced in BALB/c mice immunized with methylated bovine serum albumin in complete Freund's adjuvant by the intratracheal injection of plain agarose beads or beads conjugated to specific antigen. Large hypersensitivity granulomas developed around antigen-coupled beads in immunized animals. Smaller but still prominent granulomatous reactions developed around plain beads in immunized mice. In nonimmunized animals, both plain and antigen conjugated beads produced very small granulomas. Granuloma formation in sensitized animals was associated with suppressed delayed-type hypersensitivity reactions induced by the footpad injection of specific and nonspecific antigens. Lymph node cells from sensitized granuloma-bearing mice with cutaneous anergy showed suppressed specific and nonspecific antigen-induced proliferative responses in vitro. These cells also showed suppressed interleukin 2 production in response to specific antigen. Although no soluble suppressive factor was detected in granuloma extracts, suppressor cells were found in lymph nodes of granuloma-bearing mice, which could inhibit antigen-induced production of interleukin 2 by lymph node cells from immunized mice. Antigen-specific immunoglobulin G antibody production was not suppressed in immunized granuloma-bearing mice. Previous studies from our laboratory have demonstrated migration inhibition factor and interleukin 1 activities in aqueous extracts prepared from granuloma-bearing lungs of immunized mice. These results and the findings reported here indicate that granuloma formation and the associated anergy observed in this system are primarily expressions of cell-mediated immunity; selective suppression of in vivo and in vitro expressions of cell-mediated immunity in granuloma-bearing mice may be due to impaired antigen-induced interleukin 2 production; and such impairment is caused by suppressor cells.
Mouse skin graft prolongation with donor strain bone marrow and anti-lymphocyte serum: surface markers of the active bone marrow cells.
Authors: De Fazio S , Hartner W C , Monaco A P , Gozzo J J 
Published: December 2022

Abstract
The survival of C3H/HeJ skin grafts on B6AF1 mice treated with anti-lymphocyte serum (ALS) can be significantly prolonged by the injection of the host with C3H/HeJ bone marrow. Although the prolongation is apparently due at least in part to the ultimate presence in the host of specific suppressor cells of donor origin, little is known about the nature of the cells in the marrow inoculum that are responsible for this effect. The present investigation was undertaken to characterize surface markers of the active bone marrow cells. Marker-positive populations were either depleted and enriched by panning techniques or depleted by killing with specific antibody and complement, and then were assayed for their ability to prolong graft survival. Cells that were adherent to anti-Ia-coated plates extended graft survival only slightly better than did treatment with ALS alone, whereas nonadherent (Ia-depleted) cells, as well as cells treated with anti Ia and complement, retained good prolonging activity. Similarly, panning on anti-immunoglobulin (Ig)-coated plates produced an active, Ig+-depleted population and an inactive adherent population, and killing of Thy-1+ cells with antibody and complement did not compromise the ability of the bone marrow inoculum to prolong graft survival. Complement receptor-positive (EAC+) and Fc gamma receptor-positive cells (EA+) were separated by panning on plates coated with sheep erythrocytes/antibody/complement and erythrocytes/7S antibody respectively. Adherent, EAC+-enriched cells were only slightly active, whereas the nonadherent, EAC-depleted population was fully active in graft prolongation. However, both Fc gamma R+ (EA+)-enriched and depleted populations were active, with the enriched fraction producing significantly better prolongation than the depleted population. Thus, the bone marrow cells that can prolong skin graft survival in ALS-treated mice appear to be Ia-, Thy-1+, largely complement receptor negative, and Ig-, but are largely positive for Fc gamma receptors.
G0 B cells activated by anti-mu acquire the ability to proliferate in response to B cell-activating factors independently from entry into G1 phase.
Authors: Proust J J , Chrest F J , Buchholz M A , Nordin A A 
Published: December 2022

Abstract
In the present studies we investigated the early steps in B cell activation and determined that activation could be separated from entry into cell cycle. Purified B cells from BALB/c nu/nu mice, activated under controlled conditions by affinity-purified rabbit IgG anti-mu or F(ab')2 fragments prepared from the same antibodies, were sorted according to size by flow cytometry. Approximately 80% of the B cells were small and were shown to be in Go state by quantitative RNA analysis and by [3H]uridine and [3H]thymidine incorporation studies. The sorted Go B cells, when again incubated in serum-free medium with the appropriate anti-mu preparations, remained in Go. However, Go B cells in the presence of anti-mu have undergone significant change(s), in as much as they were now able to proliferate in response to soluble mediators. The ability to develop a proliferative response to B cell-activating factor(s), acquired independently from entry into cell cycle, characterizes another important step in early B cell activation and also indicates that Go B cells characterized on the basis of cell size, density, and/or RNA content may be in an activated state.
HLA regulates postrenal transplant CML nonreactivity.
Authors: Goulmy E , Blokland E , Persijn G , Paul L C , Wilmink J , van Rood J J 
Published: December 2022

Abstract
Previous studies have shown that lymphocytes from renal allografted patients with a good functioning graft display donor-specific cell-mediated lympholysis nonreactivity (CML-NR) in vitro. To define whether the HLA system influences the occurrence of the CML-NR, immunogenetic studies were carried out. Posttransplant lymphocytes derived from CML-NR patients were stimulated in vitro with lymphocytes from unrelated healthy blood donors, who were selected for the presence or absence of kidney donor-specific HLA antigens. The presentation of kidney donor-specific HLA-B (and -C) antigens on the lymphocytes of unrelated blood donors resulted in cytolytic nonresponsiveness, whereas presentation of the kidney donor-specific HLA-A locus antigens on lymphocytes of the unrelated blood donors revealed no cytolytic nonresponsiveness. The results, as displayed by posttransplant lymphocytes of renal allografted patients, demonstrate that the kidney donor HLA-B (and -C) antigens are responsible for the in vitro-observed, donor-specific CML-NR. Consequently, presentation of cells from panel members matched to the kidney donor at the HLA-B locus suppresses the response towards HLA-A locus antigens. The in vitro-observed cytolytic nonresponsiveness appeared not to be due to an absence of specific cytotoxic T lymphocytes, because the nonresponsiveness can be abrogated by addition of exogenous IL 2.
Noncytotoxic functions of natural killer (NK) cells: large granular lymphocytes (LGL) produce a B cell growth factor (BCGF).
Authors: Procopio A D , Allavena P , Ortaldo J R 
Published: December 2022

Abstract
Highly purified human large granular (LGL), depleted of any detectable contaminant T and B cells or monocytes, were found to be potent producers in vitro of a soluble B cell growth factor (BCGF) able to sustain proliferation of B cells activated by anti-mu. Activation by lectins (phytohemagglutinin, PHA, concanavalin A, Con A; and pokeweed mitogen, PWM) was required to induce the production of high levels of this BCGF from cultured LGL. Production of BCGF was also detected after the binding of LGL with natural killer (NK)-sensitive (K562) but not with NK-resistant (RL male 1) target cells. In contrast to T cells, LGL did not need the additional presence of accessory cells to reach optimal production of BCGF by 72 hr of culture. The subpopulation of LGL responsible for the production of BCGF had phenotypic characteristics associated with NK cells (3G8+, HNK1+/OKT11+, DR-, OKT3-, Leu-M1-), and separated cells with these markers exerted high levels of NK activity. Selective production of BCGF also was obtained from cytotoxic clones derived from LGL. A partial characterization of the LGL-derived BCGF was performed by gel filtration. BCGF activity was detected in fractions with estimated m.w. of 20,000 and 45,000. The LGL-derived BCGF activity was resistant to reduction with 2-mercaptoethanol and was stable at -20 degrees C for months. Conversely, heating (56 degrees C for 1 hr) or digestion with trypsin greatly reduced the LGL-derived BCGF activity. These findings strongly suggest that LGL including those with NK activity can play an important positive role in the early events of the B cell-mediated immune response.
Synergy between B cell differentiation factors and interleukin 2, using a monoclonal system.
Authors: Mayer L , Crow M K , Thompson C 
Published: December 2022

Abstract
By using monoclonal B cell targets, cells derived from patients with chronic lymphocytic leukemia, and B cell differentiation factors (BCDF) derived from monoclonal human T cell hybridomas, we have demonstrated marked synergy for differentiation between interleukin 2 (IL 2) and BCDF. IL 2 alone had no effect on the proliferation of differentiation to immunoglobulin secretion in these cell populations; however, in conjunction with a variety of BCDF, differentiation to plaque-forming cells (PFC) was augmented 10- to 100-fold. There was no increase in proliferation as measured by [3H]thymidine incorporation. These effects could be demonstrated with concentrations of IL 2 as low as 5 U/culture, well within the physiologic range, by using either commercially available or recombinant IL 2. The addition of IL 2 to the B cell and BCDF cultures resulted in almost 100% expression of the IL 2 receptor, Tac, on the surface of these cells, and the augmented PFC response could be inhibited 70 to 80% by the addition of anti-Tac to the culture. Kinetic studies revealed that the addition of IL 2 to the B cell cultures could be delayed for up to 72 hr without a change in the PFC response, suggesting that IL 2 was acting as a secondary or synergistic signal for differentiation. Thus, it appears that IL 2 does have a role in B cell maturation mediated, in part, by IL 2 binding to the IL 2 receptor present on certain B cells.
Assembled topographic antigenic determinants of pigeon cytochrome c.
Authors: Hannum C H , Margoliash E 
Published: December 2022

Abstract
The specificity of the IgG fraction of the sera of several rabbits hyperimmunized with glutaraldehyde-polymerized pigeon cytochrome c was examined by fluorescence-quenching titration and a sensitive competitive plate-binding radioimmunoassay developed for the analysis of small amounts of antiserum. Four pigeon cytochrome c-specific Fab fragments were found to bind simultaneously to the immunogen. Competition assays, using an extensive set of naturally occurring, chemically prepared hybrid and enzymically modified cytochromes c, implicated in antibody binding all seven amino acid residues at which the immunogen differs from the homologous rabbit cytochrome c. Thus, rabbits produce small amounts of three antibody populations directed against the regions of serine 15, alanine 44, and glycine 89, respectively, on pigeon cytochrome c, and a large amount of the population which binds to an assembled topographic determinant composed of isoleucine 3, glutamine 100, alanine 103, and lysine 104. The latter four residues are from the amino-terminal and carboxyl-terminal alpha-helices, and cluster where the two helices cross each other on the back surface of the molecule. Antibodies against native pigeon cytochrome c reacted very poorly with the several cyanogen bromide-cleaved fragments of the molecule, consisting of residues 1 to 65, 1 to 80, 66 to 104, and 81 to 104.
The B10.A mouse B cell response to pigeon cytochrome c is directed against the same area of the protein that is recognized by B10.A T cells in association with the Ek beta:Ek alpha Ia molecule.
Authors: Hannum C H , Matis L A , Schwartz R H , Margoliash E 
Published: December 2022

Abstract
An analysis of the fine specificities of the primary and hyperimmune antibody responses of B10.A mice to pigeon cytochrome c showed that both were qualitatively very similar. Small amounts of antibody appeared to be directed against the regions of serine 15 and/or glutamic acid 44. The remaining antibodies (greater than 70%) bound to the same complex topographic determinant (including residues 3, 103, and 104) on the back surface of pigeon cytochrome c which had been found to dominate the rabbit antibody response to this protein, and to be involved in Ia-restricted T cell stimulation. The mouse antibodies reacted very poorly with fragmented forms of the immunogen or with tobacco hornworm moth cytochrome c, even though both of these antigens had been shown previously to strongly stimulate pigeon cytochrome c-primed T cells. The specificities of the primary IgG responses of seven other mouse strains were found to be very similar, but not identical, to that of B10.A mice. The cytochrome c-specific antibodies in the hyperimmune serum were shown to bind to determinants involving residues that vary between pigeon and mouse cytochromes c. Comparison of the binding of the antibodies to the immunogen and to the corresponding host protein enabled the calculation of the proportion of the overall binding energy contributed by the variant residues. This was as low as 19 to 35% for the primary response, rose to 25 to 46% for the hyperimmune mouse antibodies, and reached 40 to 63% for hyperimmune rabbit antibodies. The remaining energy of interaction (37 to 81%) was necessarily contributed by the surface of the protein surrounding the variant residues, which is the same for the immunogen and the host protein. These results illustrate the relatively subtle differences in binding affinities which can distinguish self from non-self recognition by antibody molecules.
Two distinct classes of IgG Fc receptors on a human monocyte line (U937) defined by differences in binding of murine IgG subclasses at low ionic strength.
Authors: Jones D H , Looney R J , Anderson C L 
Published: December 2022

Abstract
We have defined two distinct classes of IgG Fc receptors (FcR) on cells of a human monocytic line (U937) by analyzing the direct binding of murine IgG subclasses in medium of low ionic strength. Four lines of evidence support this contention. The binding of aggregated murine IgG2b (AggmIgG2b) to U937 and Daudi cells was enhanced at low ionic strength, whereas monomeric murine IgG2a (mIgG2a) did not bind to Daudi cells and its high affinity binding to U937 cells was unaffected by changes in ionic strength. Double reciprocal inhibition experiments with U937 cells indicated that the binding of both ligands was inhibited 30 to 135 times more efficiently by the homologous ligand than by the heterologous one. That is, the binding of 125I-AggmIgG2b was inhibited 50% by 3.5 micrograms/ml of AggmIgG2b and 100 micrograms/ml of mIgG2a. Similarly, the binding of 125I-mIgG2a was inhibited 50% by 2.5 micrograms/ml of mIgG2a and only 44% by 243 micrograms/ml of AggmIgG2b. A monoclonal antibody of the IgG2b subclass raised against an IgG FcR on K562 cells inhibited binding to U937 cells of AggmIgG2b but not of mIgG2a. Trypsinization of U937 cells abrogated by 32% the binding of mIgG2a but did not affect the binding of AggmIgG2b. Human IgG inhibited binding of both AggmIgG2b and mIgG2a to U937 cells. We propose that the newly recognized FcR that binds AggmIgG2b is the human homologue of the murine macrophage IgG2b/1 FcR (FcRII), and that the previously described 72,000 dalton high-affinity FcR on U937 cells that binds mIgG2a is the human equivalent of the murine macrophage IgG2a FcR (FcRI).