bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antigen-presenting capabilities of human monocytes correlates with their expression of HLA-DS, an Ia determinant distinct from HLA-DR.
Authors: Gonwa T A , Picker L J , Raff H V , Goyert S M , Silver J , Stobo J D 
Published: December 2022

Abstract
Utilizing a monoclonal antibody (Mac-120) specific for 40 to 60% of peripheral blood adherent mononuclear cells (M phi), we were able to separate M phi into two populations based on their reactivity with the antibody. Both populations, Mac-120+ and Mac-120- cells, were then compared for a) their ability to present antigen to T cells, b) their display of HLA-DR determinants, c) their ability to stimulate in an autologous and allogeneic mixed lymphocyte reaction, and d) their display of an Ia molecule, HLA-DS, which is distinct from HLA-DR and which is homologous with murine I-A. Our findings indicate that a) only Mac-120+ cells can present antigen, b) Mac-120+ and Mac-120- cell populations are equivalent in terms of the number of HLA-DR+ cells and in the mean density of HLA-DR determinants per cell, c) although Mac-120+ and Mac-120- cells are equivalent in their ability to serve as stimulators in an allogeneic mixed lymphocyte reaction, Mac-120+ cells are better stimulators in an autologous mixed lymphocyte reaction, and d) only Mac-120+ cells display HLA-DS. These studies demonstrate that peripheral adherent mononuclear cells exhibit heterogeneity with regard to their display of Ia antigens. Furthermore, they provide functional data to support the existence of a human Ia determinant, HLA-DS, which is distinct from HLA-DR and which is important in antigen presentation and stimulation in the autologous mixed lymphocyte reaction.
Cellular interactions in marrow-grafted patients. I. Impairment of cell-mediated lympholysis associated with graft-vs-host disease and the effect of interleukin 2.
Authors: Mori T , Tsoi M S , Gillis S , Santos E , Thomas E D , Storb R 
Published: December 2022

Abstract
Forty patients with hematologic malignancy or aplastic anemia were given allogeneic marrow after conditioning with high-dose cyclophosphamide alone or in combination with total body irradiation. Between 28 and 3857 days after transplantation, their peripheral blood mononuclear leukocytes were tested for reactivity in indirect cell-mediated lympholysis against normal leukocytes from unrelated individuals, and the results were compared to those with cells from their healthy marrow donors. An impairment of cell-mediated lympholysis was found with cells from most patients with acute and chronic graft-vs-host disease (GVHD) whereas cells from most short-term and long-term patients without GVHD had cell-mediated lympholysis reactivity comparable to that of cells from the marrow donors. When interleukin 2 was added to the mixed leukocyte cultures during the sensitization phase, the impaired cell-mediated immunity of cells from most short-term patients with acute GVHD, but not that of cells from most patients with chronic GHVD, could be restored to normal levels. These results suggest the impairment of cell-mediated immunity seen in cells of short-term patients with acute GVHD is attributable to helper cell defects or to ineffective communication between antigen-presenting cells and helper T cells. The impairment in cell-mediated immunity seen in patients with chronic GVHD, however, may reside on the effector cells (or their precursors) or may be due to the presence of suppressor cell activity.
Serologic aspects of IgG4 antibodies. I. Prolonged immunization results in an IgG4-restricted response.
Authors: Aalberse R C , van der Gaag R , van Leeuwen J 
Published: December 2022

Abstract
Labeled antigen-binding tests were used to determine quantitatively the contribution of IgG4 antibodies to the total IgG antibody response in humans. In agreement with literature, we found no IgG4-restricted antibody responses with tetanus toxoid or streptococcal carbohydrate. In the serum of individuals immunized for several years with phospholipase (PLA) from honey bee venom, grass pollen allergen, or house dust mite allergen, we often found that more than 50% of the total antigen-binding capacity was due to IgG4 antibodies. In the case of beekeepers, it could clearly be shown that during prolonged immunization a shift in the IgG4:IgG1 antibody ratio occurs that finally results in an IgG4-dominated antibody response. Evidence is provided that antigen-binding assays may even underestimate the contribution of IgG4 antibodies, because in contrast to IgG1 antibodies, IgG4 antibodies act as monovalent antibodies in being unable to cross-link immunosorbent-bound antigen and radiolabeled antigen.
Antigens of Ambrosia elatior (short ragweed) pollen. III. Crossed radioimmunoelectrophoresis of ragweed-allergic patients' sera with special attention to quantification of IgE responses.
Authors: Løwenstein H , Marsh D G 
Published: December 2022

Abstract
Short ragweed allergenic extract has been studied by means of crossed radioimmunoelectrophoresis (CRIE) with the use of sera from 37 allergic patients and the relevant control sera. In this study 22 of 52 antigens, detectable in crossed immunoelectrophoresis (CIE) against polyspecific rabbit anti-ragweed IgG, were able to bind specific human IgE to their corresponding immunoprecipitates. This binding was semiquantified by comparison with the binding of a standard serum pool. Nine antigens were identified as important allergens, including the previously isolated components, AgE, AgK, and Ra6. Certain allergens (e.g., AgE, AgK, and Ag 31) bound IgE in almost all patients' sera, whereas others showed a bimodal distribution for sera of responder and nonresponder patients. The total CRIE score was found to correlate significantly both with ragweed-specific serum IgE antibody determined by RAST (rs = 0.88; p less than 0.001) and with total IgE level (rs = 0.55; p less than 0.01). Patient's CRIE scores to AgE also correlated significantly with their specific IgE antibody to AgE measured by RIA (r = 0.47; p less than 0.01) and with skin-test sensitivity to AgE (r = 0.44; p less than 0.05). It was concluded that CRIE is well suited for identification of important ragweed allergens without the previous need for laborious isolation procedures.
Generation of alloreactive cytotoxic T lymphocytes: evidence for a differentiation factor distinct from IL 2.
Authors: Finke J H , Scott J , Gillis S , Hilfiker M L 
Published: December 2022

Abstract
In this report we provide evidence that the generation of cytotoxic T lymphocytes (CTL) involves a differentiation signal in addition to a proliferative signal, and that the differentiation signal is mediated by a factor distinct from interleukin 2 (IL 2). Generation of CTL from nylon wool-nonadherent splenocytes stimulated by heat-treated thymocytes did not correlate with the addition of IL 2-containing supernatants to this factor-dependent bioassay. IL 2 from two different sources and prepared by different methods (purified IL 2 from the LBRM33 cell line and partially purified IL 2 from the EL4 cell line) was not sufficient to generate a cytotoxic response in the bioassay. The inability of IL 2 to generate a cytotoxic response was not due to the use of heat-treated stimulator cells because similar results were obtained with UV-treated cells. As we previously reported, supernatant fluids containing a differentiation/activation factor did generate CTL from nylon wool-nonadherent splenocytes. Supernatant fluid from co-cultures of activated T cells and M phi as well as from cultures of activated M phi contained this CTL helper factor; however, only the former supernatant contained IL 2 activity. These results suggest a factor distinct from IL 2 is providing a differentiation/activation signal that is necessary for CTL development. Although IL 2 was not effective at generating CTL from nylon wool-nonadherent splenocytes, it was capable in some, but not all, experiments of generating a cytotoxic response from unseparated splenocytes. The ability of IL 2 to induce a cytotoxic response from unseparated splenocytes appeared to correlate with the presence of a weak background response seen when unseparated cells were used as responder cells.
Limiting dilution analysis of the frequency of human T cells and large granular lymphocytes proliferating in response to interleukin 2. II. Regulatory role of interferon on proliferative and cytotoxic precursors.
Authors: Vose B M , Riccardi C , Bonnard G D , Herberman R B 
Published: December 2022

Abstract
Limiting dilution analysis has shown that large granular lymphocytes (LGL) and small T cells undergo proliferation in response to lectin-free IL 2. The latter is critically dependent on prior stimulation with lectin. Depending on conditions, alpha or beta interferons (IFN) were found to have either of two opposing effects on the frequency of proliferating cells. Pretreatment of responder cells with IFN resulted in dose-dependent augmentation of proliferative progenitors such that at 500 IU/ml, a fivefold increase of progenitor frequency was apparent. Under such conditions, approximately 5% of LGL could be expanded, and at least a proportion of the cultured cells killed the NK-sensitive K562 cell line. Similar results were apparent with T cell responders: whatever the initial frequency of proliferation (dependent on the PHA dose), augmentation was obtained with IFN pretreatment, although no killing of K562 was induced. In contrast, when IFN was present throughout the 7-day assay period, proliferative frequencies were reduced. This inhibitory effect was mediated through the presence of irradiated T cells in the feeder populations. With purified monocytes as feeder cells, little reduction was seen, whereas addition of T cells resulted in a 19-fold inhibition. Separation of OKT4+ and OKT8+ subsets demonstrated that both were essential for optimum induction of suppression. These data indicate that IFN has a powerful immunodulatory role on both NK and T cell proliferation, and that it may function both by induction of IL 2 receptors and activation of suppressive T cells. The interaction between different soluble mediators provides a complex immunoregulatory circuit in vitro.
Staphylococcus aureus protein A induces the production of interferon-alpha in human lymphocytes and interferon-alpha/beta in mouse spleen cells.
Authors: Smith E M , Johnson H M , Blalock J E 
Published: December 2022

Abstract
Human and mouse lymphocytes produced IFN-alpha and IFN-alpha/beta, respectively, when incubated with highly purified Staphylococcus aureus protein A (SPA). Maximum IFN induction occurred when lymphocytes were incubated with SPA at 250 to 500 micrograms/ml for 24 hr. The SPA induced-IFN were identified by neutralization of antiviral activity with specific antisera. A commercial preparation of SPA was found to induce both HuIFN-alpha and HuIFN-gamma, with the latter comprising over 90% of the antiviral activity. The SPA preparation that induced IFN-gamma was shown by SDS-polyacrylamide gel electrophoresis and an enzyme-linked immunosorbent assay to be contaminated with 5% S. aureus enterotoxin A (SEA), a potent T lymphocyte mitogen and IFN-gamma inducer. Preincubation of the commercial SPA with a specific antiserum to SEA blocked the induction of IFN-gamma and had no effect on IFN-alpha production. SEA is a very potent IFN-gamma inducer, effective at concentrations of 1 ng/ml or less. Thus, very minor contamination of SPA by SEA or other IFN-gamma inducers could be responsible for previous reports that SPA induces IFN-gamma in lymphocytes or that SPA behaves as a T cell mitogen.
A newly defined murine alloantigen controlled by the S region of the H-2 complex: molecular association with the fourth component of complement.
Authors: Spinella D G , Passmore H C 
Published: December 2022

Abstract
A previous study has shown that prolonged immunization of strain A.TBR16 mice (H-2 haplotype at16) with lymphoid tissue derived from A.TBR13 (at13) donors results in an antiserum that defines a new H-2-associated allotype with a strain distribution antithetical to H-2.7. The present report describes a sensitive ELISA that demonstrated that this specificity represents an allotypic determinant(s) on the fourth component of complement (C4). Studies with Sephadex G-200 fractionated plasma and serum proteins suggest that, as is the case for H-2.7, the new specificity appears to reside on the C4d fragment after C activation. We therefore propose the tentative nomenclature C4d.2 for this specificity and suggest revision of the nomenclature for H-2.7 to C4d.1. Also described in this report is the formal mapping of the genetic control of the C4d.2 allotype to the H-2S region.
Immune enhancement in mice by ara-A.
Authors: Hinrichs J , Kitz D , Kobayashi G , Little J R 
Published: December 2022

Abstract
Ara-A in single, apparently nontoxic doses stimulates murine immune responses to several well-defined antigens. Both humoral and cell-mediated responses are enhanced by ara-A, but not all mouse strains respond equally well. In certain mouse strains, ara-A also promotes increased (or decreased) survival during experimental infection with Cryptococcus neoformans, suggesting that clinically significant effects on host resistance may result from the use of ara-A as an antiviral therapeutic agent. The biochemical mechanisms of action of the aranucleosides suggest that the immunostimulation produced by ara-A depends on suppressor cell toxicity.
Hormonal activation of adenylate cyclase in macrophage membranes is regulated by guanine nucleotides.
Authors: Verghese M W , Snyderman R 
Published: December 2022

Abstract
Many macrophage functions such as chemotaxis, phagocytosis, enzyme secretion, and cytotoxicity are influenced by intracellular cyclic nucleotide levels, but the regulatory mechanisms involved are poorly defined. We have developed methods that allowed us to study the activation of AC in isolated guinea pig (g.p.) macrophage membranes. AC in these membrane preparations could be stimulated approximately twofold by guanine nucleotides. We could not obtain any hormonal activation of membrane-bound AC in the absence of guanine nucleotides. In the presence of GTP, however, the hormones isoproterenol and PGE1 elicited an additional threefold rise in AC activity, which subsided after approximately 15 min. As little as 10(-8) M concentrations of these two hormones induced significant elevations of AC activity. Replacement of GTP by its nonhydrolyzable analogue Gpp(NH)p resulted in a persistent hormone-independent activation of AC, and addition of hormones enhanced this level of activation. Thus, GTP-ase activity is present in macrophage membrane preparations and serves to regulate AC activation. Hormonal stimulation of AC was receptor mediated, because the effect of the beta-adrenergic agonist isoproterenol, but not PGE1, was inhibited by the beta-adrenergic blocker propranolol. In addition, the potency series of PG corresponded to that observed for stimulation of cAMP production in intact g.p. macrophages, i.e., PGE1 = PGE2 greater than PGA1 greater than PGF2 alpha. AC activation by PG in the membrane preparation was inhibited by an alpha-adrenergic agonist, thus demonstrating one means for down regulating cAMP production in g.p. macrophages. Our studies also showed that certain hormones (e.g., beta-adrenergic agonists, PG) can exert their effect on cAMP production by stimulation of membrane-bound AC, whereas other agents such as lectins or arachidonic acid require additional intracellular components to elevate cAMP levels in macrophages. The mechanism of activation of AC by hormones in g.p. macrophage membranes appears to fit the model of a ternary complex, the components of which include the hormone receptor, AC, and guanine nucleotide regulatory protein, which transmits the signal from the receptor to AC.
A new lymphocyte cell surface antigen, Ly-22.2, controlled by a locus on chromosome 4 and a second unlinked locus.
Authors: Meruelo D , Offer M , Flieger N 
Published: December 2022

Abstract
A serum raised by immunizing (B10.A(4R) X B10.HTT)F1 mice against A.AL lymphocytes detects a new antigenic determinant designated Ly-22.2. Ly-22.2 expression is under the control of two independently segregating genes, one of which maps to chromosome 4 adjacent to a locus affecting XenCSA expression. Ly-22.2 is present in varying amounts in all lymphoid organs, but appears to be expressed primarily on T lymphocytes. Ly-22.2 is not detectable in brain, kidney, lung, liver, or erythrocytes. Strain distribution studies show Ly-22.2 is present in all strains examined except B10-derived congenic strains. It is of interest that C57BL/6 and C57BL/10 mice differ in the expression of this antigen.
Influence of dietary restriction and aging on natural killer cell activity in mice.
Authors: Weindruch R , Devens B H , Raff H V , Walford R L 
Published: December 2022

Abstract
Natural killer cells (NK) are believed to defend against tumor growth. Because rodents subjected to dietary restriction without malnutrition live longer and develop spontaneous tumors less often or later in life than unrestricted controls, we measured NK activity in restricted and in unrestricted mice. An age-related decline in NK responses to YAC-1 tumor target cells was detected in both groups. NK responses for control mice were highest in 2- to 3-mo-old mice, sharply reduced in middle-age mice (14 to 15 mo), and slightly reduced further in old mice (30 to 33 mo). At all ages the response of restricted mice was less than that of controls. However, after injection with Poly I:C (which increases NK activity), old restricted mice showed NK cytolysis not different from young mice on either diet, and substantially higher responses than old unrestricted mice. In addition, restricted mice showed increased in vitro generation of cytotoxic T lymphocytes (CTL) to YAC-1 and P815 compared with age-matched controls. Restricted mice may better resist cancer via an NK system very responsive to induction signals coupled with a CTL system more effective than that of unrestricted controls.
Pteridines as a new marker to detect human T cells activated by allogeneic or modified self major histocompatibility complex (MHC) determinants.
Authors: Huber C , Fuchs D , Hausen A , Margreiter R , Reibnegger G , Spielberger M , Wachter H 
Published: December 2022

Abstract
Evidence is presented that activation of T cells by allogeneic or modified autologous cells leads to the specific production of two distinct molecular compounds of the PT class. One of these two PT has previously been identified as neopterin. The structure of the other is still under investigation. This conclusion was based on the following findings: a) In vitro both PT were produced by T cells proliferating in response to HLA incompatible allogeneic or to autologous EB-virus-transformed or TNP-haptenized cells. b) In vitro stimulation of T cells with mitogenic lectins or protein antigens, of macrophages with zymosan-complement, of B cells with PWM or EB-virus, and of NK effector cells with tumor targets failed to induce comparable release of these PT. c) In vivo increased amounts of both PT were excreted via the urine during allograft rejection and viral infections. It thus appears that the production of these PT is primarily a feature of activated T cells involved in the control of self integrity.
T cell regulation of B cell activation: antigen-specific and antigen-nonspecific suppressor pathways are mediated by distinct T cell subpopulations.
Authors: Asano Y , Hodes R J 
Published: December 2022

Abstract
The present studies were carried out to characterize the cellular events involved in the induction and function of carrier-specific Ts cells, which selectively regulate the generation of IgG responses by Lyb-5- B cells. It was demonstrated that this regulation is in fact mediated by two distinct suppressor pathways. In one pathway, carrier-primed Lyt-1 + 2 - Ts cells are specifically activated by in vitro reexposure to the priming antigen. After this specific activation, these Lyt-1 + 2 - Ts cells are able to suppress IgG responses in an antigen-nonspecific manner. This suppression requires the participation of unprimed Lyt-1 - 2 + T cells, and is effective in both the early and the late phases of antibody responses. A second suppressor pathway requires the antigen-specific activation of primed Lyt-1 - 2 + Ts cells. Suppression of antibody responses by activated Lyt-1 - 2 + Ts cells is highly carrier specific, in contrast to the nonspecific effector function of Lyt-1 + 2 - Ts cells, appears to act without requirement for additional T cell populations; and is effective only early in the course of the antibody response. Thus, it appears that two Ts cell populations may function through distinct mechanisms to regulate the generation of IgG Lyb-5- B cell responses.
The origin of cytotoxic T lymphocyte precursors (CTL-P): MHC-restricted and alloreactive CTL-P in the spleen during regeneration after a sublethal dose of cyclophosphamide (Cy).
Authors: Sihvola M , Hurme M 
Published: December 2022

Abstract
The regenerating spleen 8 days after an injection of a sublethal dose (300 mg/kg) of cyclophosphamide (Cy) had a defective capacity to give rise to cytotoxic T lymphocytes (CTL) in response against allogeneic cells, whereas the cytotoxicity against 2,4,6-trinitrophenyl-(TNP) modified syngeneic cells was at the normal level. Alloresponse was first obtained 2 wk after the Cy treatment. The limiting dilution analysis showed this at the clonal level: the frequency of anti-TNP-specific CTL precursors (CTL-P) in the spleen treated with Cy 8 days previously was the same as the frequency in the normal spleen. The defective alloresponse was due to a decreased number of allospecific CTL-P that was later increasing. The regenerative capacity was not abolished by adult thymectomy or treatment of the mice with a bone marrow-seeking isotope, 89Sr, suggesting that these CTL-P are derived from Cy-resistant splenic precursors rather than from the thymus or bone marrow. These precursors have probably been under thymic education: the dominance of H-2k-restricted CTL over H-2d-restricted CTL in the response of (H-2k X H-2d)F1 mice to TNP-self is known to be influenced by the H-2 genotype of the thymus, and this dominance was also demonstrated with anti-TNP CTL derived from these F1 mice pretreated with Cy. The CTL-P in the regenerating spleen (day 8) were not hydrocortisone sensitive, and nylon wool-purified T cells from this stage had a lactate dehydrogenase (LDH) isoenzyme pattern of the mature T cell type (rather than of the thymocyte type). Thus, in these aspects the T cells of the regenerating spleen resembled normal splenic cells. These data suggest that the Cy-resistant spleen population contains cells that can give rise to CTL-P that have a defective specificity repertoire at the beginning of the regeneration, but later mature to a normally alloreactive population.