bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-tumor activity of class II MHC antigen-restricted cloned autoreactive T cells. I. Destruction of B16 melanoma cells mediated by bystander cytolysis in vitro.
Authors: Shiohara T , Ruddle N H , Horowitz M , Moellmann G E , Lerner A B 
Published: December 2022

Abstract
Two Lyt-1+, L3T4a+ autoreactive T cell clones specific for self-class II major histocompatibility complex (MHC) gene products were established from lymph node cells and spleen cells of C57BL/6J mice, respectively, by different methods. They were stimulated to proliferate in culture in response to I-Ab antigen-bearing syngeneic spleen cells in a class II MHC-restricted manner. This stimulation was inhibited completely by the addition of anti-L3T4a (GK1.5) or anti-I-Ab (3JP) monoclonal antibodies. The autoreactive T cell clones lysed syngeneic I-Ab+ target cells such as lipopolysaccharide (LPS) blasts. They also lysed I-A- bystander cells such as Cloudman and B16 melanoma and lymphoid tumor cells in the presence of I-Ab+ stimulator cells but not I-Ad+ cells. This bystander killing was most likely mediated by soluble factors released from the autoreactive T cells in response to I-Ab antigens, because culture supernatants from activated autoreactive T cells inhibited the proliferation of B16 melanoma cells in vitro and also had significant cytolytic activity. Both lymphotoxin and interferon-gamma were released from activated autoreactive T cells, suggesting that these cytotoxic lymphokines were responsible for autoreactive T cell-mediated cytolysis. The finding that the two clones, established independently and by different methods, show self-class II MHC antigen-restricted cytolysis, and bystander cytolysis suggests that these properties are not restricted to a unique population of autoreactive T cells. These results favor the concept that in vivo, autoreactive T cells may express not only regulatory activity in regard to antibody responses, but also anti-tumor activity via bystander cytolysis.
Anti-tumor activity of class II MHC antigen-restricted cloned autoreactive T cells. II. Novel immunotherapy of B16 melanomas by local and systemic adoptive transfer.
Authors: Shiohara T , Moellmann G , Jacobson K , Kuklinska E , Ruddle N H , Lerner A B 
Published: December 2022

Abstract
Lyt-1+, L3T4a+ autoreactive cloned T cells, producing lymphotoxin (LT) and interferon-gamma (IFN-gamma) in response to self-class II major histocompatibility complex antigen in vitro were examined for their anti-tumor effect in vivo against B16 melanomas. Without the aid of exogenous interleukin 2, the autoreactive T cells, when injected immediately and at an equal cell number into the site of s.c. inoculated B16 melanoma cells inhibited tumor growth in sublethally irradiated and nonirradiated syngeneic mice. The autoreactive T cells also induced regression of tumors established 3 days earlier. Normal spleen cells or class II-restricted cloned T cells specific for chicken gamma-globulin (CGG) had no inhibitory effect on tumor growth. A single injection of autoreactive T cells delayed tumor growth and prolonged the survival of mice that had received a lethal dose of B16 melanoma cells. The autoreactive T cells caused extensive necrosis at the injection site. A treatment regime consisting of two successive injections of anti-I-Ab monoclonal antibody 3JP prevented the inhibition of tumor growth, supporting the hypothesis that the autoreactive T cells inhibited the growth of melanomas by releasing LT and IFN-gamma upon recognition of I-A antigen-bearing cells at the injection site. The CGG-specific control T cells did not cause necrosis and survived within the nests of uninhibited tumor cells. Autoreactive T cells administered i.v. immediately after i.v. injection of B16 melanoma cells markedly reduced pulmonary metastases, whereas CGG-specific T cells did not. These results indicate that autoreactive T cells can function in vivo as inhibitors of tumor growth.
Antibody-dependent cellular cytotoxicity mediated by murine lymphocytes activated in recombinant interleukin 2.
Authors: Shiloni E , Eisenthal A , Sachs D , Rosenberg S A 
Published: December 2022

Abstract
The incubation of murine splenocytes in recombinant interleukin 2 (RIL 2) gives rise to lymphokine-activated killer (LAK) cells that can lyse fresh, NK-resistant tumor cells but not normal cells in 4-hr 51Cr-release assays. Lysis by this IL 2-activated cell population was enhanced up to 100-fold by prior reaction of target cells with specific antisera reactive with antigens on the target cells. This antibody-dependent cellular cytotoxicity (ADCC) also resulted in lysis of fresh normal target cells, which are not usually susceptible to LAK lysis. The ADCC was evident after 24 hr of incubation of splenocytes in RIL 2, but peak lytic activity was reached after 3 to 4 days of incubation. The concentrations of RIL 2 needed for the in vitro activation of the effectors in order to attain maximal ADCC was between 100 and 3000 U/ml and parallel the IL 2 concentrations required to generate LAK cells. ADCC mediated by IL 2-activated splenocytes was completely blocked by anti-FcR monoclonal antibodies. Although antisera directed against MHC antigens were used in most experiments, anti-B16 monoclonal antibodies have also shown the ability to induce ADCC mediated by RIL 2-activated syngeneic and allogeneic cells. Treatment of the precursor splenocyte populations with anti-asialo GM1 and complement eliminated the direct LAK activity and the antibody-dependent cytotoxicity, suggesting that both direct and indirect tumor cell lysis may be caused by the same effector cell. ADCC mediated by LAK cell populations represents another possible mechanism for the in vivo therapeutic effects of these cells.
Expression of Leu-19 (NKH-1) antigen on IL 2-dependent cytotoxic and non-cytotoxic T cell lines.
Authors: Lanier L L , Le A M , Ding A , Evans E L , Krensky A M , Clayberger C , Phillips J H 
Published: December 2022

Abstract
The Leu-19 (NKH-1) antigen is expressed on human peripheral blood NK cells and a subset of peripheral blood cytotoxic T lymphocytes that kill "NK-sensitive" tumor cell targets without major histocompatibility complex restriction. In the present study, we demonstrate that the Leu-19 (NKH-1) antigen is also expressed on most interleukin 2 (IL 2) dependent T cell lines and clones that have been maintained in long term culture. The Leu-19 (NKH-1) antigen expressed on an antigen-specific, class I directed cytotoxic T lymphocyte cell line was an approximately 200,000 to 220,000 dalton protein, similar to Leu-19 (NKH-1) protein expressed on natural killer cells and KG1a, an immature stem cell leukemia cell line. Furthermore, Leu-19 (NKH-1) was expressed on both CD4+ and CD8+ IL 2 dependent T cell clones, and was present on both cytotoxic and non-cytotoxic T cell clones. Thus expression of Leu-19 (NKH-1) antigen on cultured cell lines does not directly correlate with cytotoxic function, antigenic specificity, or cell lineage.
Intracellular growth of Listeria monocytogenes as a prerequisite for in vivo induction of T cell-mediated immunity.
Authors: Berche P , Gaillard J L , Sansonetti P J 
Published: December 2022

Abstract
The in vivo induction of T cell-mediated immunity was studied by infecting mice with two genetically closely related mutants from Listeria monocytogenes, differing only with respect to the secretion of an active SH-dependent hemolysin. It is shown that even minute doses of hemolytic bacteria capable of growing in host tissues easily induced the expression of T cell-mediated immunity, as estimated by the level of delayed sensitivity, adoptive protection and long-lasting immunological memory. On the contrary, nonhemolytic bacteria unable to multiply in host tissues totally failed to initiate the expression of T cell-mediated immunity in vivo. This failure was even observed when mice were repeatedly infected by high doses of nonhemolytic bacteria, allowing to maintain a significant amount of viable bacteria for several days in host tissues. These results mean that the presence of viable bacteria at a significant level in the host is not sufficient per se to induce detectable T cell clonal expansion in the in vivo setting, implying that the process of bacterial growth inside macrophages is required to initiate in vivo the expression of T cell-mediated immunity.
Start of mu-chain production by the further two-step rearrangements of immunoglobulin heavy chain genes on one chromosome from a DJH/DJH configuration in an Abelson virus-transformed cell line: evidence of secondary DJH complex formation.
Authors: Maeda T , Sugiyama H , Tani Y , Miyake S , Oka Y , Ogawa H , Komori T , Soma T , Kishimoto S 
Published: December 2022

Abstract
A variant was selected from an Abelson virus-transformed cell line with identifiable and distinguishable DJH rearrangements on both chromosomes. Southern blotting experiments suggested that this variant resulted from a secondary DJH complex formation accompanied with the deletion of one of the DJH rearrangements on the same chromosome. Furthermore, this variant started making mu-chains by the further functional join of a VH gene to the secondarily formed DJH complex. Thus, we describe here the first evidence of a secondary DJH complex formation.
Development of host-dependent high-grade tumor-specific immunity through a novel mechanism triggered by the Lyt-2+ tumor-specific T cell clone (K7L) that induces temporal growth of L1210 leukemia-K7L-variant.
Authors: Nagase F , Ueda K , Kawashima K , Jamshedur Rahman S M , Isobe K , Yoshida T , Hasegawa Y , Ando K , Iwamoto T , Nagura E 
Published: December 2022

Abstract
When a murine leukemia L1210-specific Lyt-2+ T cell clone, K7L, was injected i.p. into CD2F1 mice together with L1210, the normal growth of L1210 in the peritoneal cavity of the mice at the early stage (days 0 to 5) was strongly inhibited, but L1210 grew progressively at the middle-stage (days 5 to 10), and then was rejected at the late stage (days 10 to 20). The mice thus survived for long times (more than 60 days), whereas the normal control injected with L1210 alone died within 14 days. The L1210 that grew at the middle stage in mice initially inoculated with L1210 together with K7L was a K7L-insensitive (K7L-) variant. All of eight tumor clones established from L1210-K7L- by limiting dilution was insensitive to the antitumor activity of K7L, and this property of tumor clones was stable after repeated in vitro passage. The initial depression of the L1210 growth by K7L followed by growth and rejection of the variant L1210-K7L- by the host T cell activity was then found to prepare a strong, long-lasting (more than 3 mo) immunity to protect mice against the high-dose (10(7) cells per mouse) challenge of original L1210. Corresponding to this result, definite tumor (L1210)-specific cytotoxic T lymphocyte (CTL) activity against both variant and original L1210 targets was developed by antigen (L1210) restimulation in the culture of spleen cells from these mice, but was not increased to a detectable level before L1210-K7L- variant started to grow. It was suggested that the 1210-K7L- variant and the original L1210 should have the common tumor-specific antigen that was independent of the K7L-reactive antigen, and that original L1210, whose growth was retarded by K7L, primed the host with the common antigen to be enormously boosted by the subsequently growing L1210-K7L- variant.
Participation of L3T4 in T cell activation in the absence of class II major histocompatibility complex antigens. Inhibition by anti-L3T4 antibodies is a function both of epitope density and mode of presentation of anti-receptor antibody.
Authors: Owens T , Fazekas de St Groth B 
Published: December 2022

Abstract
The recognition of many class II major histocompatibility complex (MHC)-associated antigens by T cells requires the participation of the L3T4 molecule. It has been proposed that this molecule acts to stabilize low affinity binding to antigen in association with MHC and thereby increases the avidity of T cell/antigen interactions. By using antibodies against the T cell antigen receptor (TCR) to activate T cells, thereby circumventing the requirement for antigen presenting cells and MHC-associated antigen, we have been able to study the function of L3T4 in the absence of class II MHC. We have used two monoclonal antibodies, KJ16-133.18 and F23.1, that recognize a determinant encoded by the T cell receptor V beta 8 gene family. These antibodies were used to select two clones of T cells with surface phenotype Thy-1.2+, L3T4+, Lyt-2-, KJ16-133.18+, F23.1+, IA-, IE-. One of these clones (E9.D4) was hapten-specific (anti-ABA + Iak), the other (4.35F2) was alloreactive (anti-Iak). Activation of these clones by antigen, concanavalin A (Con A) or by the F23.1 antibody was studied by assaying the production of interleukin 3 (IL 3). Both soluble and solid phase-coupled F23.1 induced T cell activation in the complete absence of class II MHC, immobilized antibody (either Sepharose-coupled or plastic-adsorbed) being more effective. The induction of IL 3 production by suboptimal doses of either Con A or plastic-adsorbed F23.1 was inhibited by the anti-L3T4 antibody GK1.5, as was the response to F23.1 coupled to Sepharose-4B beads. However, the responses to optimal or superoptimal doses of these stimuli were not inhibited. In contrast, weak responses to non-TCR cross-linking stimuli such as phorbol myristate acetate (PMA) or low concentrations of soluble F23.1 were not inhibited by GK1.5 (the latter response was usually slightly enhanced). These results show that anti-L3T4 antibodies are not inherently inhibitory, but require both ligation and cross-linking of the TCR for their effect. We propose a model whereby L3T4 interacts with the TCR during T cell activation. Anti-L3T4 antibodies sterically hinder the formation of TCR complexes and so prevent activation. However, by increasing the epitope density of the activating ligand, the avidity of the T cell/ligand interaction can be increased sufficiently to prevent this disruption.(ABSTRACT TRUNCATED AT 400 WORDS)
Role of the transferrin receptor in lymphocyte growth: a rat IgG monoclonal antibody against the murine transferrin receptor produces highly selective inhibition of T and B cell activation protocols.
Authors: Kemp J D , Thorson J A , McAlmont T H , Horowitz M , Cowdery J S , Ballas Z K 
Published: December 2022

Abstract
We have produced a new rat IgG monoclonal antibody against the murine transferrin receptor (TR). This antibody (C2F2) exhibits a surprisingly selective pattern of inhibition of murine lymphocyte activation protocols. C2F2 inhibits the mixed lymphocyte reaction (MLR) and the generation of cytotoxic T cells. Interestingly, although interleukin 1 (IL 1)-dependent thymocyte co-stimulatory activity is strongly inhibited by C2F2, interleukin 2 (IL 2)-dependent thymocyte co-stimulation is only marginally reduced. IL 2-dependent growth of CTLL cells is also not inhibited by C2F2. These data suggest that IL 1-dependent helper T cell activation is very sensitive to C2F2-mediated inhibition. Studies with phytohemagglutinin, Concanavalin A, and lipopolysaccharide induced activation also indicate that the inhibitory effects of C2F2 are selective, and T cell activation may be more sensitive to inhibition than B cell activation. Although there is little published information about the functional effects of other rat anti-mouse TR antibodies, the available data suggest that the patterns of inhibition produced by anti-TR antibodies may be individually distinct. Anti-TR antibodies may constitute a new set of highly selective probes for the study of lymphocyte activation.
Autoantibodies against a specific nuclear RNP protein in sera of patients with autoimmune rheumatic diseases associated with myositis.
Authors: Arad-Dann H , Isenberg D A , Shoenfeld Y , Offen D , Sperling J , Sperling R 
Published: December 2022

Abstract
Polymyositis is an autoimmune, inflammatory disease affecting human skeletal muscle. In the presence of concomitant vasculitis in the skin, the term dermatomyositis is used. In contrast, systemic lupus erythematosus (SLE) is a multisystem disease in which involvement of the skin, kidneys, joints, brain, and other organs may be found. The clinical manifestations vary according to the organ/system involved. It is clinical and therapeutic importance to define which organ/system is involved during the course of the disease. We approached this problem by studying the specificity of autoantibodies that are generated in patients with SLE and polymyositis/dermatomyositis. Among such antibodies are those directed against nuclear components including a variety of ribonucleoprotein (RNP) complexes. We have utilized mammalian nuclear preparations enriched with RNP particles as the antigenic source for immunoblotting studies to identify specific antigenic polypeptides. In the study reported here, sera from five groups of patients were examined: 10 patients with dermatomyositis/polymyositis; six patients with SLE and myositis; 12 lupus patients with cerebral and/or renal disease; eight patients with SLE but no myositis, renal, or cerebral disease; and 5) 11 patients with muscle weakness or muscle disease not due to myositis. In the first two groups of patients with myositis, antibodies against a nuclear RNP protein of 56 KD was identified in 12 of 16 sera. In contrast, such antibodies were found in the serum of only two of 20 patients with SLE but without muscle involvement (groups 3 and 4), and were not found at all in patients with other muscle diseases. This study has identified a new marker, antibodies against a nuclear RNP protein of 56 KD for detecting muscle involvement among the autoimmune rheumatic diseases.
Characterization of immunologic and neuropathologic abnormalities in wasted mice.
Authors: Woloschak G E , Rodriguez M , Krco C J 
Published: December 2022

Abstract
Mice bearing the autosomal recessive gene "wasted" (wst/wst) have been reported to develop low or absent secretory immune responses, abnormal DNA repair mechanisms, and uncoordinated body movements. We have performed a detailed immunologic and neuropathologic investigation of the disease. Con A and LPS mitogenic responses of splenic lymphocytes as well as total serum Ig levels were equivalent in wst/wst and undiseased control littermates (wst/+ and +/+). Amounts of serum IgM, IgG2a, IgG2b, IgG3, and IgA, however, were reduced in wst/wst animals. FACS analyses of Ig+ and isotype-specific B cell populations revealed similar percentages of Ig+, mu +, gamma +, and alpha + cells in wst/wst and control mice. However, the percentage of "very bright" Ig+ cells as well as "very bright" heavy and light chain-specific B cell subpopulations was increased at least 10-fold in wst/wst B cells as compared with littermate controls. In addition, studies of Ig-specific mRNA accumulation in these animals revealed significant decreases in all isotypes except gamma 3 in spleens of wst/wst mice as compared with littermate controls. Neuropathologic studies in wst/wst mice showed prominent vacuolar degeneration of neurons within anterior horns of the spinal cord and the motor nuclei of the brain stem. No abnormalities were noted in Purkinje cells of the cerebellum nor within myelin sheaths. The abnormalities in the nervous system resembled human motor neuron disease rather than ataxia-telangiectasia as had been reported previously. The immunologic studies suggest that splenic B cells from wst/wst mice have a defect in the ability to "switch" from membrane to secreted Ig. In addition, this mutation provides a mechanism to study regulatory interactions between the immune and nervous systems.
C1q inhibits the expression of B lymphoblastoid cell line interleukin 1 (IL 1).
Authors: Habicht G S , Beck G , Ghebrehiwet B 
Published: December 2022

Abstract
Although the existence and ubiquity of the C1q receptor is well established, its role in health and disease is largely unknown. Interleukin 1 (IL 1) is the major immunoregulatory molecule produced by macrophages and B lymphoblastoid cell lines. In this paper we present evidence that occupancy of C1q receptors by C1q on B lymphoblastoid cell lines inhibits "IL 1-like" activity, which is constitutively produced by these cells. When 5 X 10(6) Raji cells were cultured (24 hr at 37 degrees C) in the presence or absence of various concentrations of C1q (final concentration; 5 to 50 micrograms/ml) and the cellfree supernatants were analyzed for their effect on thymocyte proliferation by using the concanavalin A co-mitogenesis assay for IL 1, a statistically significant dose-dependent reduction of 3H-TdR incorporation was observed. Similar results were obtained when Daudi and Wil2WT cells were used, whereas Molt4, which is a T cell lymphoblastoid cell line, neither produced "IL 1-like" activity nor was affected by C1q. When immune complex-bound C1q was used instead of free C1q, inhibition of B cell IL 1 activity was also observed. Mixing experiments showed that Raji cells incubated with C1q released an inhibitor of IL 1-induced thymocyte proliferation. C1q alone had no effect on thymocyte proliferation in the presence or absence of human IL 1. In addition, the effect of C1q on IL 1 activity was abrogated either when the C1q was heat inactivated (56 degrees C, 60 min) or when the C1q was incubated with the cells in the presence of F(ab')2 anti-C1q. On the basis of these data, it is concluded that B cell receptor-bound C1q may play an important role in immunoregulation.
Quantitation of histamine, tryptase, and chymase in dispersed human T and TC mast cells.
Authors: Schwartz L B , Irani A M , Roller K , Castells M C , Schechter N M 
Published: December 2022

Abstract
Levels of histamine, chymase, and tryptase were assessed in preparations of dispersed human TC (tryptase+, chymase+) mast cells obtained from foreskin and of dispersed human T (tryptase+, chymase-) mast cells obtained from lung. Consistent with previous immunohistochemical results, extracts of T mast cells, the predominant mast cell type in lung (93% T and 7% TC mast cells), were deficient in human chymase (less than 0.3 microgram and 0.04 U/10(6) mast cells) but not tryptase (10.8 micrograms and 0.3 U/10(6) mast cells) by corresponding immunologic and enzymatic (suc-L-ala-ala-pro-phe-p-nitroanilide in the presence of aprotinin and tosyl-L-gly-pro-lys-p-nitroanilide in the presence of soybean trypsin inhibitor, respectively) assays. The minor presence of chymase activity in lung could be accounted for by the minor presence of lung TC mast cells. Extracts of TC mast cells, the predominant mast cell type (1% T and 99% TC mast cells) in foreskin, contained both proteases. However, TC mast cells from adult foreskin contained eightfold to 10-fold higher levels of chymase (4.5 micrograms and 1.01 U/10(6) mast cells) and twofold to threefold higher levels of tryptase (11.5 micrograms and 0.27 U/10(6) mast cells) than did TC mast cells from newborn foreskin (less than 0.6 microgram and 0.09 U of chymase and 35 micrograms and 0.62 U of tryptase/10(6) mast cells). In contrast, histamine levels were not significantly different in adult foreskin TC (1.9 microgram/10(6) mast cells), newborn foreskin TC (1.6 microgram/10(6) mast cells), and adult lung T (1.5 microgram/10(6) mast cells) mast cells. The relative ratio of each mediator in newborn foreskin mast cells to that in adult foreskin mast cells is highest for histamine, followed by tryptase and then chymase. Tryptase from TC and T mast cells had identical subunit compositions by Western blot analysis and similar apparent specific activities. This study extends the previously reported immunohistochemical distinction between human T and TC mast cells in tissue sections by direct quantitation of chymase and tryptase in dispersed preparations of T and TC mast cells.