bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sodium periodate-induced T cell mitogenesis: an analysis of the requirement for Ia and IL 1.
Authors: Smith L A , Cohen D A , Lachman L B , Kaplan A M 
Published: December 2022

Abstract
T lymphocytes oxidized with the mitogen sodium periodate undergo a proliferative response when cultured in the presence of Ia+ accessory cells. However, the exact role(s) the accessory cells play in such a response has not been clearly defined. We have evaluated the role of Ia and the requirement for interleukin 1 (IL 1) in periodate mitogenicity by using the Ia+ cloned tumor cell lines P388AD (Ia+, IL 1 inducible) and P388NA (Ia+, IL 1 noninducible) as accessory cells. P388AD but not P388NA was able to supply accessory cell function to periodate-treated T cells, suggesting that Ia expression alone was not sufficient to reconstitute a response. Monoclonal anti-I-Ad and anti-I-Ed antibody blocked the accessory cell function of P388AD. In addition, monoclonal antibody GK 1.5, directed against the T cell determinant L3T4a, blocked the P388AD/periodate-treated T cell interaction, confirming that this interaction was restricted by class II molecules. Although Ia expression was required, the response was not major histocompatibility complex (MHC) restricted, because allogeneic as well as syngeneic macrophages were capable of supplying accessory cell function to periodate-treated T cells. Exogenous IL 1 alone was able to trigger periodate-treated T cells, suggesting that Ia was required for the induction of IL 1 synthesis by the accessory cells. Furthermore, purified IL 2, devoid of IL 1 activity, was able to fully reconstitute the proliferative response of accessory cell-depleted oxidized T cells to a level equal to that of whole spleen accessory cells or P388AD. These data suggest that periodate-treated T cells can proliferate with IL 1 alone and that Ia+ accessory cells in periodate-mediated T cell mitogenicity may function in the release of IL 1 and the induction of IL 2 synthesis by the T cells.
The role of arachidonic acid metabolism in the activities of interleukin 1 and 2.
Authors: Farrar W L , Humes J L 
Published: December 2022

Abstract
Several investigations have suggested that products of arachidonic acid metabolism have modulatory effects on the development of cellular immunity. In this report we have studied the role of arachidonic acid metabolism in the specific effects of interleukin 1 (IL 1) induction of interleukin 2 (IL 2), and also IL 2 stimulation of proliferation and interferon-gamma (IFN-gamma) production. Utilizing cell lines that are specifically responsive to IL 1 or IL 2, it was found that both interleukins stimulate lipoxygenation of arachidonic acid in their respective target cell. The ability of each interleukin to induce monohydroxyeicosatetraenoic acid (HETE) correlated with the induction of secondary lymphokine secretion. Utilizing selective and partially selective pharmacologic inhibitors of arachidonic acid metabolism, the data suggest that the participation of lipoxygenase activity is required for both IL 1 induction of IL 2 production and IL 2 regulation of proliferation and IFN-gamma secretion. The same requirement for lipoxygenase activity was seen when phorbol myristate acetate (PMA) was used as a secretory stimulant, suggesting a similar mode of action for stimulation-secretory activity between PMA and interleukins. Studies performed with an endogenous inhibitor of 5-lipoxygenase (15-HETE) demonstrated the requirement of this enzyme system for IL 2-dependent proliferation and IFN-gamma production. Although leukotrienes could replace IL 2 for IFN-gamma secretion, they had no effect on IL 2 growth promotion. The results suggest that both IL 1 and IL 2, and PMA, may share the lipoxygenase pathway of arachidonic acid metabolism which is a component of the intracellular signal transduction process that regulates secretory activity and/or cellular proliferation.
Selective improvement of thymus and some T cell dysfunctions in NZB mice by in utero thymulin treatment.
Authors: Quéré P , Dardenne M , Bach M A 
Published: December 2022

Abstract
NZB mice were treated during gestation with thymulin, a thymus-secreted, zinc-associated nonapeptide. Control pregnant NZB mice received either zinc alone or saline alone. Offspring from all three groups of NZB mothers, and age-matched DBA/2 mice, were tested for the following immunologic parameters: thymulin serum levels at 2 and 5 wk of age; splenic anti-sheep red blood cell (anti-SRBC) plaque-forming cell (PFC) numbers after immunization at birth or at 2 wk of age; anti-human gamma-globulin (anti-HGG) antibody titers after immunization at 2 wk of age, with or without prior tolerance induction at birth with deaggregated HGG; spontaneous IgM serum levels at 2 and 5 wk of age; spontaneous splenic anti-trinitrophenyl (anti-TNP) PFC numbers at 2 wk of age. As compared with DBA/2 mice, young NZB mice exhibited low circulating thymulin titers, high antibody responses to SRBC and to HGG, resistance to tolerance induction by deaggregated HGG, increased spontaneous IgM serum levels, and increased spontaneous anti-TNP PFC numbers. However, marked reductions in anti-SRBC and anti-HGG antibody production, both thymus-dependent responses, were observed in the young NZB offspring of thymulin-treated mothers as compared with NZB controls born from zinc- or saline-treated mothers. A delay in the postnatal decrease of serum thymulin levels was also noted in the offspring of thymulin-treated mothers. Interestingly, these effects of in utero thymulin treatment tended to become more pronounced with advancing age during the postnatal period. Conversely, IgM serum levels, spontaneous anti-TNP PFC and sensitivity to tolerance induction were not affected by thymulin treatment during fetal life. Taken together, the data suggest that in utero exposure to pharmacologic concentrations of thymulin induces a persistent and selective improvement of some thymus and T cell dysfunctions but has no effect on intrinsic B cell abnormalities of NZB mice.
Structural analysis of the myeloma-associated membrane antigen KMA.
Authors: Goodnow C C , Raison R L 
Published: December 2022

Abstract
kappa-Myeloma antigen (KMA) was immunoprecipitated from lactoperoxidase-radioiodinated HMy2 lymphoblastoid cells by using monoclonal antibody K-1-21 and was analyzed by SDS-PAGE. Under reducing conditions, two major subunits of Mr approximately 26,000 and Mr approximately 42,000, and minor components of Mr approximately 28,000, 31,000, and 36,000 were observed. The Mr approximately 26,000 subunit was identical to kappa-light chains from HMy2 surface IgG in apparent m.w., isoelectric point, and staphylococcal V-8 protease peptide map, but was not precipitated in association with Ig heavy chain. The Mr approximately 42,000 component was homologous to rabbit skeletal muscle actin by peptide mapping with staphylococcal V-8 protease. The cell surface origin of the immunoprecipitated antigen was confirmed by demonstrating lactoperoxidase dependence of iodination and complete removal from the cell surface after pronase treatment of viable cells. Thus, cell surface expression of KMA is the result of membrane association of non-heavy chain-linked kappa-light chains, possibly in noncovalent association with actin.
Characterization of the beta-adrenergic receptor of the rat peritoneal macrophage.
Authors: Abrass C K , O'Connor S W , Scarpace P J , Abrass I B 
Published: December 2022

Abstract
The beta-adrenergic receptor was characterized on BCG-activated rat peritoneal macrophage membranes by radio-ligand binding studies. Saturable binding with [125I]iodocyanopindolol (125I-ICYP) was demonstrated. With Scatchard analysis, rat macrophages demonstrate approximately 1000 receptors per cell with a Kd of 5 X 10(-11) M for 125I-ICYP. Competition curves with (-) and (+) propranolol at concentrations below 10(-6) M confirmed stereospecificity. The potency of various ligands to compete for 125I-ICYP binding sites followed the order: propranolol greater than isoproterenol greater than epinephrine greater than norepinephrine with apparent Kd of 2.0 X 10(-9), 3.9 X 10(-7), 1.0 X 10(-5), and 2.5 X 10(-5) M, respectively. Isoproterenol-stimulated adenylate cyclase activity was two-fold above basal activity. The potential physiologic significance of a beta-adrenergic receptor on rat peritoneal macrophages was suggested by a dose-dependent decrease in phagocytosis of soluble, model immune complexes (aggregated gamma-globulin) by macrophages incubated with metaproterenol. We conclude that the rat macrophage has a beta-adrenergic receptor and that catecholamines may thereby modulate macrophage function.
A synthetic decapeptide of influenza virus hemagglutinin elicits helper T cells with the same fine recognition specificities as occur in response to whole virus.
Authors: Hackett C J , Hurwitz J L , Dietzschold B , Gerhard W 
Published: December 2022

Abstract
The immunogenicity of an isolated murine helper T cell determinant was studied. Mice were immunized with a synthetic peptide corresponding to amino acid residues 111-120 of the influenza PR8 hemagglutinin (HA) heavy chain, a region previously identified as a major target of the helper T cell response to the HA molecule in virus-primed BALB/c mice. Lymph node T cells from these mice were fused with BW 5147 cells to produce T hybrids for clonal analysis of their recognition specificities. Three T cell hybridoma clones, obtained from two different mice, responded to the immunizing peptide when presented by syngeneic antigen-presenting cells. All of these clones responded also to antigen provided as intact wild-type PR8 virus. The fine specificity of the peptide-induced T cell hybridomas, in response to a panel of mutant and variant influenza viruses, was indistinguishable from the fine specificities of T cells to the corresponding region of the HA1 chain of the HA molecule which had been generated by priming of mice with intact wild-type virus. These results suggest that an immunogenic determinant is contained within the 111-120 sequence that is able to elicit anti-influenza virus T cells with a similar repertoire to those elicited by immunization with whole virus.
Defective cell-mediated immunity in leprosy: failure of T cells from lepromatous leprosy patients to respond to Mycobacterium leprae is associated with defective expression of interleukin 2 receptors and is not reconstituted by interleukin 2.
Authors: Mohagheghpour N , Gelber R H , Larrick J W , Sasaki D T , Brennan P J , Engleman E G 
Published: December 2022

Abstract
Patients with lepromatous leprosy (LL) but not borderline tuberculoid leprosy (BT) have defective cell-mediated immune responses to Mycobacterium leprae, despite normal responses to other stimuli, as judged by in vivo skin testing and in vitro lymphocyte transformation. To investigate the basis of the immune defect in LL patients, we studied the ability of patient mononuclear leukocytes to produce interleukin 1 (IL 1) and interleukin 2 (IL 2) upon stimulation with M. leprae, and determined the ability of exogenous IL 1 and IL 2 to reconstitute the LL patient response to this antigen in vitro. Equal numbers of adherent non-T cells from LL and BT patients produced similar amounts of IL 1 upon challenge with M. leprae, and addition of IL 1 to the culture medium failed to reconstitute the response of lymphocytes from LL patients to M. leprae. On the other hand, T cells of LL patients failed to express receptors for IL 2 or to produce IL 2 in response to M. leprae, whereas similarly treated T cells of BT patients both expressed IL 2 receptors and produced IL 2. Finally, recombinant human IL 2 purified to homogeneity as well as crude supernatants of mitogen-activated lymphocytes failed to reconstitute the response of LL patients to M. leprae. These results suggest that T cells of LL patients fail to respond to M. leprae despite an ability to produce IL 1 and that their failure to express receptors for IL 2 may explain both defective proliferation and the failure of exogenous IL 2 to reconstitute the response.
The mechanism of human NK cell-mediated cytotoxicity. Mode of action of surface-associated proteases in the early stages of the lytic reaction.
Authors: Lavie G , Leib Z , Servadio C 
Published: December 2022

Abstract
The possible involvement of cell surface-associated proteolytic enzymes in human NK cell-mediated cytotoxicity and the mechanism by which such enzymes exert their activity have been studied. The treatment of intact cells with 3H-DFP under restricted conditions that predominantly bind surface-associated enzymes resulted in the labeling of five to six enzyme bands. Among these were a 35,000-dalton enzyme, which may be a previously identified trypsin-like proteinase engaged in cytotoxicity, and a 58,000-dalton elastase. The latter seems not to be involved in the reaction, as potent inhibitors of this enzyme have negligible effect on cytotoxicity. Of the membrane-associated enzymes, those engaged in cytotoxicity seem to be concealed from the external environment, as pretreatment of the effector cells with protease inhibitors such as trasylol and PMSF have no effect on the reaction. Immediately upon addition of the target cells and the initiation of cytotoxicity, the reaction becomes highly sensitive to inhibitors for a limited time interval of 2 to 5 min when trasylol is employed and 5 to 10 min when TPCK is the inhibitor, suggesting that target cell binding triggers the exposure of the enzymes to the external environment, rendering them accessible to the inhibitors. This short sensitivity period parallels the interval in which the reaction is sensitive to the microfilament inhibitor cytochalasin B. As the reaction proceeds, it becomes increasingly resistant to inhibitors of both proteolysis and cytoskeleton, at the same time suggesting that microfilament action and the unraveling of proteases may be processes that bear a close linkage with one another. The surface-associated elastase on the other hand maintains a constitutive mode of activity distinctive and unrelated to that of enzymes engaged in cytotoxicity. These findings suggest the existence on the surface of the NK lymphocyte of a mechanism that associates the receptor for target cells with an array of enclaved proteolytic enzymes via microfilaments. The resting cytotoxic structures become activated as the receptor attaches to the target cell, triggers the exposure of the proteolytic moiety, and initiates the lytic phase of the reaction.
Systemic administration of recombinant interleukin 2 stimulates in vivo lymphoid cell proliferation in tissues.
Authors: Ettinghausen S E , Lipford E H , Mulé J J , Rosenberg S A 
Published: December 2022

Abstract
Recent work in our laboratory has demonstrated that the repeated injections of high doses of recombinant interleukin 2 (IL 2) can dramatically reduce the number of established pulmonary and hepatic metastases and the growth of intradermal tumors in a variety of murine tumor models. We have thus undertaken studies to define the mechanisms underlying these in vivo effects of IL 2. Using an in vivo DNA-labeling technique in which we employed 5-[125I]iodo-2'-deoxyuridine (125IUdR), we examined the in vivo cell proliferation in the tissues of mice treated with IL 2. A proliferation index (PI) was calculated by dividing the raw counts per minute (cpm) of tissues in IL 2-treated mice by the cpm in corresponding tissues of control animals. At an IL 2 dose of 6000 U given i.p. three times a day, the highest 125IUdR incorporation was seen in the lungs, liver, spleen, kidneys, and mesenteric lymph nodes (PI = 6.9, 6.9, 5.1, 7.1, 24.6, respectively, at 5 days). The amount of lymphoid proliferation in these organs was a direct function of the dose of IL 2 administered. Other tissues including thymus, intestines, skin, and hind limb showed no significant increase in 125IUdR uptake even after host treatment with the highest doses of IL 2. Blood and brain demonstrated intermediate incorporation of the radiolabel. Preirradiation of the host largely eliminated the proliferative response to IL 2. Histologic studies of normal and irradiated mice receiving IL 2 corroborated the result of the 125IUdR findings. In normal IL 2-treated mice, large collections of activated lymphoid cells were seen, most prominently in the lungs, liver, and kidneys, whereas markedly decreased lymphoid proliferation was evident histologically in preirradiated mice. A fluorescein-labeled monoclonal antibody directed against the Thy-1.2 surface determinant was used to identify these dividing cells in frozen tissue sections as T lymphoid cells. Activated lymphocytes isolated from the lungs, liver, spleen, and mesenteric lymph nodes of IL 2-treated mice demonstrated significant lysis of a fresh murine sarcoma target in short-term 51Cr-release assays. These studies demonstrate that the systemic administration of recombinant IL 2 causes in vivo activation and proliferation of host lymphoid cells and has important implications for the adoptive immunotherapy of tumors.
Amplification of immune T lymphocyte function in situ: the identification of active components of the immunologic network during tumor rejection.
Authors: Evans R , Duffy T M 
Published: December 2022

Abstract
Previous data had indicated that sarcoma-bearing mice receiving combination therapy consisting of a single i.p. injection of cytoxan (CY) and an i.v. injection of tumor-sensitized T cells (immune cells) rejected the neoplasm. The reaction was immunologically specific and dependent on donor T cells. This report is concerned with the hypothesis that the transfer of immune cells results in the amplification of T cell responses at the tumor site. Using C57BL/6J mice bearing the syngeneic rhabdomyosarcoma MCA/76-9, we show that 6 to 9 days after combination therapy those components usually associated with the immunologic network were present at the tumor site. Tumor-associated macrophages (TAM) and lymphocytes (TAL) were shown to produce IL 1 and IL 2, respectively. The TAM expressed Ir gene products (Ia) and were able to present the synthetic polymer GAT to specifically sensitized lymphocytes. In addition, it was demonstrated by in situ labeling with 3H-TdR that lymphocytes associated with the regressing tumors were proliferating. The peak incorporation occurred 7 days after therapy, 24 hr before a significant increase in the T cell content of the tumors. The data indicate that those facets of the immunologic network necessary for amplification were present at the site of rejection.
Multiple epitopes on human and murine cells expressing HLA-B7 as defined by specific murine cytotoxic T cell clones.
Authors: Yannelli J R , Moore L C , Engelhard V H 
Published: December 2022

Abstract
Eleven cytotoxic T lymphocyte (CTL) clones were derived from C57BL/6 spleen cells immunized with HLA-B7 expressing human lymphoblastoid cell lines. Reactivity against HLA-B7 was initially established because the clones lysed 2 target cells that shared only HLA-B7 with the immunizing cell line and they did not lyse five other cell lines that were HLA-B7 negative but expressed other class I or class II antigens found on the immunizing cell. Six of the clones were subsequently shown to lyse all tested HLA-B7-positive B and T lymphoid cell lines, peripheral blood lymphocytes, and a murine L cell that expressed HLA-B7 as a consequence of DNA-mediated gene transfer. On the basis of the inability of the clones to lyse a panel of HLA-B7-negative cell lines, up to 18 other class I antigens could be eliminated as being cross-reactively recognized. However, two of the clones recognized a single HLA-B7-negative cell line. It is suggested that in these cases the clones were cross-reactively recognizing the HLA-B27 or HLA-B40 antigens that were present on these target cells. The remaining five CTL clones failed to lyse one out of seven tested HLA-B7-positive lymphoid lines (either RPMI-1788 or DR1B) and failed to lyse peripheral blood lymphocytes from one out of three tested HLA-B7-positive individuals. These five clones also did not recognize the HLA-B7-positive murine L cell. However, based on analysis with a large target cell panel, the reactivity pattern of these five clones could only be correlated with recognition of HLA-B7. This conclusion is further supported by antibody-blocking studies to be reported elsewhere. As before, lysis of single HLA-B7-negative target cells by two of the clones could be ascribed to recognition of HLA-B27 or HLA-B40. The results show that murine clones raised against HLA-B7 exhibit a high degree of specificity for determinants that are unique or largely confined to the HLA-B7 alloantigen. In addition, these clones define different antigenic determinants on the molecule. Thus, such clones appear to be excellent candidates for use as human tissue typing reagent. The results further show that there is a strong correlation between recognition of particular HLA-B7-positive human cell lines and recognition of the HLA-B7 expressing murine L cell. Possible reasons for such a correlation and their relationship to the general phenomenon of CTL recognition are discussed.
Transplantation of cultured thymic fragments. VI. H-2 recombinant donors.
Authors: Jenski L J , Hong R 
Published: December 2022

Abstract
Athymic (nude) mice were transplanted with cultured thymic fragments from syngeneic, allogeneic, and partially allogeneic (recombinant) mice. Lymphocyte proliferation and cytotoxicity in vitro were measured to assess immunologic reconstitution. Transplanted nude mice were immunocompetent whether donor and recipient were disparate for class I, class II, or both H-2 gene types. Furthermore, allotolerance for thymic H-2 class I antigens was achieved independently of class II antigen allotolerance. Class I antigen tolerance was not broken during lymphocyte responses to unrelated alloantigens, ruling out insufficient help as the tolerance mechanism. Splenocytes, isolated from nude mice transplanted with fully allogeneic or syngeneic thymic fragments and stimulated in vitro with trinitrophenyl-modified cells, displayed H-2-restricted, hapten-specific cytotoxicity. Cytotoxic cells from allotolerant mice were restricted to either host or thymic H-2 antigens, depending on the stimulating cell haplotype. Response levels for thymic and host trinitrophenyl-modified cells were comparable. We have shown that allogeneic thymic epithelium transplanted into adult nude mice can induce allotolerance to class I and II H-2 antigens equally, and permits T lymphocyte interaction with cells bearing thymic donor or host H-2 antigens. Our results are consistent with a model wherein T lymphocyte self-receptors retain their genomic repertoire but can be selectively mutated or expanded by appropriate H-2 antigen presentation by the thymus.