bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of cytotoxic T lymphocytes requires at least two spleen cell-derived helper factors besides interleukin 2.
Authors: Falk W , Männel D N , Dröge W 
Published: December 2022

Abstract
The dependency of induction of T cell cytotoxicity on lymphokines was studied. 1 X 10(5) nylon wool-purified thymic lymphocytes or 10(4) spleen cells were cultured with TNP-haptenated syngeneic UV-irradiated spleen cells in the presence of a variety of lymphokine preparations. Concanavalin A-induced spleen cell supernatants mediated strong cytotoxic responses in this system. Three other preparations, namely, a partially purified IL 2 preparation from PMA-stimulated EL-4 thymoma cells, a Con A-induced spleen cell supernatant that was absorbed with an IL 2-dependent cell line, and a Con A-induced supernatant that was dialyzed at pH 2 were all ineffective in mediating a cytotoxic response. In reconstitution experiments, cytotoxic responses were only obtained when either the absorbed preparation or the pH 2-treated preparation was mixed with the IL 2 preparation from EL-4 cells. No reconstitution occurred after mixing of the absorbed with the pH 2-treated preparation. pH 2 treatment of the absorbed preparation did not abolish its synergistic effect when added to the IL 2 preparation from EL-4 cells. These results led to the conclusion that activation of cytotoxic lymphocyte precursors requires at least two other lymphokines in addition to IL 2. One T cell cytotoxicity-inducing factor (TCF1) remained in Con A-induced supernatants after absorption with IL 2 receptor-bearing T cell line cells. It was pH 2-resistant and was not found in EL-4 supernatants. A second T cell cytotoxicity-inducing factor (TCF2) was pH 2-sensitive and was found in Con A-induced spleen cell supernatants as well as in interferon-free supernatants of PMA-stimulated EL-4 cells. This activity co-purified with IL 2. It was absorbed by the IL 2-dependent T cell line together with IL 2. IL 2 differs from TCF2 since it is pH 2-resistant.
Phorbol myristate acetate and in vitro T lymphocyte function. II. Influence of PMA and supernatants from PMA-treated P388D1 cells on the proliferation of cloned T cells.
Authors: Orosz C G , Roopenian D C , Bach F H 
Published: December 2022

Abstract
Neither the culture supernatants from P388D1 cells pulsed with phorbol myristate acetate (PMA), nor PMA itself in concentrations ranging from 10(-6) M to 10(-9) M, are directly mitogenic for murine T lymphocyte clones, yet both markedly augment the antigen-driven proliferation of many, but not all, cloned T lymphocytes. The component of PMA-induced P388D1 supernatant responsible for its co-mitogenic activity is probably PMA, rather than interleukin 1. For responsive clones, the co-mitogenic effect of PMA requires stimulator cells that display the specific allogeneic determinants recognized by the clones. This response persists after T cells are removed from the stimulating population, ruling out induction of mitogenic lymphokines from stimulator T cells by PMA as a primary mechanism for augmentation of clonal proliferation. Both splenocytes and thymocytes cooperate with PMA for enhanced clonal expansion, but heat treatment (45 degrees C, 45 min) of thymocytes destroys their cooperative capacity. PMA can also potentiate the lymphokine-driven proliferation of cloned T cells, indicating that PMA can, under certain conditions, influence T cell clonal expansion by a direct action on T lymphocytes.
Characterization of a suppressor cell-activating factor (SCAF) released by adherent cells treated with M. tuberculosis.
Authors: Wadee A A , Mendelsohn D , Rabson A R 
Published: December 2022

Abstract
Peripheral blood adherent cells ingesting killed Mycobacterium tuberculosis release a suppressor cell-activating factor (SCAF) into their culture supernatants. When adherent cells ingested 125I-labeled M. tuberculosis, radioactivity could be detected in the supernatant within 2 hr. When this supernatant was fractionated on a Sepharose 2B column, the fraction with suppressor cell-activating activity was also found to contain the majority of the radiolabel, which suggests that the macrophage processed bacteria (or bacterial product) constituted the major portion of the SCAF. This fraction also contained a high proportion of lipid, and the fraction with suppressor activity resided purely within the phospholipid fraction. By employing thin layer chromatography, the phospholipids responsible were identified as phosphatidylethanolamine and phosphatidylinositol. These results indicate that when macrophages ingest mycobacteria, they release phosphatidylethanolamine and phosphatidylinositol of bacterial origin into their culture supernatants, which are responsible for activating suppressor T cells.
Binding of phosphatidylethanolamine and phosphatidylinositol to OKT8+ lymphocytes activates suppressor cell activity.
Authors: Wadee A A , Rabson A R 
Published: December 2022

Abstract
The phospholipids phosphatidylethanolamine (PE) and phosphatidylinositol (PI) have been shown to activate a population of OKT8-enriched lymphocytes to become activated suppressor cells that result in the suppression of lymphocyte blastogenesis to a variety of mitogens and antigens. This suppression is dose dependent, and maximal suppressor activity is obtained at concentrations of 125 micrograms/ml PE and 25 micrograms/ml PI. Activation of the suppressor cell population is not associated with an actual increase in the number of cells expressing the OKT8 antigen, but the number of these cells expressing Dr antigens on their surface was increased. Both PE and PI bound to lymphocytes in a specific manner. Binding of radiolabeled PE could be inhibited by unlabeled PE but not by PI or phosphatidylserine (PS). Similarly, the binding of PI to lymphocytes was also found to be specific. Although radiolabeled PE bound to lymphocytes other than OKT8+ cells, and to other peripheral leukocytes, it bound to OKT8+ cells with a significantly greater affinity than it did to the other cell types. The Kd for PE was 1 x 10(2) nM and for PI was 1 x 10(3) nM, and receptor cell densities for these two phospholipids were estimated at 1 x 10(-8) nM and 3 x 10(-9) nM, respectively. The receptors for these two phospholipids were trypsin and heat sensitive, and the receptor sites could be regenerated after a 24-hr incubation after trypsinization.
Studies of antigen binding on human basophils. II. Continued expression of antigen-specific IgE during antigen-induced desensitization.
Authors: MacGlashan D , Mogowski M , Lichtenstein L M 
Published: December 2022

Abstract
We previously postulated that desensitization of human basophils was due to endocytosis or shedding of IgE and/or its Fc receptor. We report here, however, that during a 3-hr desensitization of purified basophils, there was no loss of cell surface antigen-specific IgE. The specific desensitization induced by antigen persists for at least 24 hr whereas simultaneously occurring nonspecific desensitization can recover during the same time interval. Therefore, we suggested that specific desensitization may result from a permanent modification of the Fc receptor or some closely associated protein. On the basis of elution studies of 125I-labeled BPO-HSA, we also suggest the antigen antibody reaction matures to aggregates of increasing size, and we propose that these large aggregates, unable to initiate a release signal, cause an additional component of desensitization.
Inactivation of human high molecular weight kininogen by human mast cell tryptase.
Authors: Maier M , Spragg J , Schwartz L B 
Published: December 2022

Abstract
Tryptase, the major neutral protease of human pulmonary mast cell secretory granules, rapidly inactivates human high m.w. kininogen (HMWK) in vitro. HMWK (5600 nM) lost 50% of its capacity to release kinin in response to kallikrein after a 5-min incubation with tryptase (31 nM), even though kinin activity was neither generated nor, when bradykinin was incubated with tryptase, destroyed by tryptase. The procoagulant activity of HMWK (51 nM) and the purified procoagulant chain (40 nM) that is derived from HMWK were each 72% inactivated after 7 min of incubation with tryptase (0.04 nM and 0.02 nM, respectively). Human urinary and pancreatic kallikrein did not inactivate this procoagulant activity under conditions in which kinin generation occurs. Complete cleavage of native single-chain HMWK by tryptase occurred in less than 10 min as analyzed by electrophoresis in sodium dodecyl sulfate polyacrylamide slab gels. The major products formed during the initial 2 min were proteins of 100,000 and 95,000 apparent m.w., and by 10 to 30 min were fragments of 74,000 and 67,000 apparent m.w. Reduction of these cleavage products yielded two major fragments of 67,000 and 66,000 apparent m.w. that were both present by 0.17 min. The presence of lower m.w. products, thought to be primarily from the carboxy-terminal procoagulant region of HMWK, were also detected with and without reduction. The capacity of tryptase to inactivate HMWK is consistent with the ability of other mast cell-derived mediators, such as heparin proteoglycan and prostaglandin D2, to suppress blood coagulation and thrombosis, and may play an important role in the biology of mast cell-dependent events in vivo.
Induction of immune responses by schistosome granuloma macrophages.
Authors: Sunday M E , Stadecker M J , Wright J A , Aoki I , Dorf M E 
Published: December 2022

Abstract
In mice, granuloma formation after Schistosomiasis mansoni infection is known to be a T cell-dependent response to schistosome eggs that peaks at 6 to 8 wk after infection (early) then regresses to a minimum by 20 to 32 wk (late). This decline in host responsiveness, termed modulation, has been attributed to T cell-mediated suppression. We now have investigated the macrophages from either Early or Late schistosome granulomas phenotypically and found no difference in expression of I-A subregion encoded antigens. We also tested granuloma macrophage (Gm) populations in their capacity to induce positive and negative antigen-specific immune responses to the hapten 4-hydroxy-3-nitrophenyl acetyl (NP). As few as 10(3) to 10(4) NP-coupled Early or Late Gm given s.c. were equally capable of inducing MHC-restricted NP-specific delayed-type hypersensitivity (DTH) responses and this DTH-inducing capability was equivalent to that of splenic adherent cell (SAC) controls. Further, both Early and Late Gm were able to generate NP-specific induction-phase suppressor cells (Ts1) when as few as 10(2) NP-coupled Gm were given i.v., the same as NP-SAC controls. Finally, NP-specific effector-phase suppressor cells (Ts3) were equally induced by Early Gm, Late Gm, or SAC controls. Therefore, macrophages derived from Early or Late schistosome granulomas or normal spleens are apparently phenotypically indistinguishable and equally capable, in extremely small quantities, of inducing NP-specific DTH, Ts1, and Ts3 immune responses.
Phorbol ester mediates reversible reduction of cloned T lymphocyte cytolysis.
Authors: Orosz C G , Roopenian D C , Bach F H 
Published: December 2022

Abstract
Prolonged contact with nanomole to micromole concentrations of the tumor promoter phorbol myristate acetate causes a significant reduction in the lytic activity of cloned cytolytic T cells. Diminished lysis is apparent even in the presence of agglutinating lectins. PMA does not exert this effect by minimizing clone viability. In fact, these concentrations of PMA cause significant potentiation of antigen-driven proliferation for many of these same clones. The PMA-mediated loss of cytolysis is reversible. Although contact with antigen does not induce or enhance reexpression of cytolysis, PMA-treated cytolytic T cell clones display normal cytolytic activity after contact with lymphokines.
Interleukin 2-dependent natural killer (NK) cell lines from patients with primary T cell immunodeficiencies.
Authors: Flomenberg N , Welte K , Mertelsmann R , O'Reilly R , Dupont B 
Published: December 2022

Abstract
Bulk cultured cell lines with natural killer (NK) activity were derived by in vitro culture with interleukin 2-containing conditioned medium (IL 2-CM) of peripheral blood mononuclear leukocytes (PBL) from patients with primary T cell deficiencies. Lines were developed from three patients with severe combined immunodeficiency (SCID) and one patient with Nezelof's syndrome and contained several populations of cells with distinct phenotypes. All lines contained a cell population expressing the Leu-5 (50K) (sheep red blood cell receptor), 3A1 (40K), and OKT10 antigens, but lacking the pan T cell antigens Leu-1 (67K) and Leu-4 (19K) as well as the markers of T cell subsets Leu-2a (32K) and Leu-3a (56K). These cells failed to express the Leu-7 antigen and only weakly expressed OKM1. In addition, one line contained a population of Leu-5+, 3A1+, OKT10+, Leu-2a+, Leu 1-, and Leu 4- cells. Three of the lines also contained populations with classic T cell (Leu-1 and-Leu 4+) phenotypes. The lines were enriched in NK activity compared with the PBL from which they were derived. Their growth was strictly dependent on IL 2-CM. Highly purified IL 2, lacking any other detectable protein contaminants or lymphokine activities, was capable of supporting the growth of the Leu-5+, 3A1+ "null" cell populations from these lines without alteration in their functional activity or phenotype. Thus, studies of in vitro expanded cell lines from patients with severe disorders of T cell function and thymic involution indicate that this "null" cell population does not require thymic maturation to develop its effector function. This "null" cell population can be maintained in vitro in the presence of IL 2. This finding is analogous to the data obtained from study of NK cells in athymic (nude) mice.
Defective production of interleukin 1 and interleukin 2 in patients with systemic lupus erythematosus (SLE).
Authors: Linker-Israeli M , Bakke A C , Kitridou R C , Gendler S , Gillis S , Horwitz D A 
Published: December 2022

Abstract
The objective of this study was to define some causes of the immunologic impairment characteristic of systemic lupus erythematosus. Blood mononuclear cells from 19 patients were stimulated to produce interleukin 1 and interleukin 2 and compared with controls. A severe defect in both IL 1 and IL 2 activity was observed. The low cytokine levels did not correlate with clinical or serologic activity of disease. These defects could not be explained by concurrent corticosteroid therapy. There was no correlation between a lower number of OKT4+ cells observed in these patients and the levels of IL 2 production, nor did removal of monocytes bring IL 2 to normal. Impaired IL 2 production could not be restored to normal by IL 1. The observed deficiency in these regulatory cytokines may therefore be a primary defect that is important in the pathogenesis of this disorder.
Immunopathology of murine experimental allergic orchitis.
Authors: Kohno S , Munoz J A , Williams T M , Teuscher C , Bernard C C , Tung K S 
Published: December 2022

Abstract
Experimental allergic orchitis (EAO) was induced consistently in BALB/c mice by immunization with homologous testicular tissue homogenate emulsified in complete Freund's adjuvant (CFA) providing that the animals had received simultaneously at least 1 microgram of an extract of Bordetella pertussis rich in pertussigen. All animals thus treated developed orchitis and serum antibody to testicular antigens within 20 days after immunization. The lesions were located in testis (100%), rete testis (37%), cauda epididymis (21%), and vas deferens (37%). Ductus efferentes and caput epididymis were only rarely affected. Early lesions in the seminiferous tubules were characterized by peritubular and/or intratubular accumulation of eosinophils, neutrophils, lymphocytes, and macrophages. This was followed by aspermatogenesis. Late lesions included massive necrosis and extensive fibrosis of the seminiferous tubules. Disruption of blood-testis barrier on day 20 was evidenced by the detection of 1) perfused lanthanum deposits between Sertoli cells and surrounding inflammatory cells inside the seminiferous tubules, 2) deposits of endogenous mouse IgG in germinal epithelium, and 3) probable immune complexes (granular C3) surrounding seminiferous tubules. Murine EAO differed from that of the guinea pig in the lack of involvement of the ductus efferentes, the extensive necrosis, the abundant polymorphonuclear eosinophils in the lesion, and the exquisite requirement of concomitant injection of B. pertussis extract.
Attempts at standardization of lupus-like graft-vs-host disease: inadvertent repopulation by DBA/2 spleen cells of H-2-different nonirradiated F1 mice.
Authors: Van Rappard-Van Der Veen F M , Radaszkiewicz T , Terraneo L , Gleichmann E 
Published: December 2022

Abstract
By induction of a suitable graft-vs-host reaction (GVHR) in nonirradiated, H-2-incompatible F1 mice, one can induce a syndrome strongly resembling systemic lupus erythematosus (SLE). The aim of the present study was to standardize the kind and number of DBA/2 donor cells required for optimal induction of this SLE-like GVH disease (GVHD). Groups of adult (C57BL/10 x DBA/2)F1 (BDF1) mice were injected i.v. with increasing numbers of DBA/2 spleen and lymph-node cells. We found that doses of 100 x 10(6) to 180 x 10(6) spleen and lymph-node cells provided a suitable donor-cell inoculum, whereas doses of donor cells below 100 x 10(6) were suboptimal and doses higher than 180 x 10(6) cells were supraoptimal for the induction of SLE-like GVHD. In a number of those F1 recipients that had received the donor-cell inocula composed of spleen cells, the duration of autoantibody formation was surprisingly brief. This appeared to be due to the fact that these GVH F1 mice were rapidly repopulated by lympho-hemopoietic donor cells. Even after the highest doses of DBA/2 spleen and lymph-node cells administered, this repopulation was not preceded by symptoms of acute GVH disease. Repopulation was avoided and a severe SLE-like disease induced when a mixture deficient in hemopoietic cells, i.e., 280 x 10(6) DBA/2 lymph-node and thymus cells, was used as donor-cell inoculum. Taken together, we reached three conclusions. First, the induction of full-blown SLE-like GVHD depends not only on the injection of a sufficient number of donor T cells but also on the continuous presence of F1 lymphoid cells, which seem to serve as stimulator cells. Second, in addition to the lymphoid hyperplasia and immune-complex glomerulonephritis (ICGN) described previously, the GVHR-induced lesions presenting themselves in the context of SLE-like autoimmunity include a Sjögren-like lymphoid infiltration of the salivary gland, a ubiquitous periarteritis, and a lymphoid infiltration of the bile ducts that is reminiscent of primary biliary cirrhosis. Third, the repopulation by donor cells of nonirradiated, H-2-incompatible hosts need not be accompanied by GVH mortality or symptoms of acute GVHD.
Dependency of human T lymphocyte colony formation on soluble factors produced by accessory or tumor cells.
Authors: Winkelstein A 
Published: December 2022

Abstract
When plated in agar, PHA-stimulated Ficoll-Hypaque separated human mononuclear cells readily form discrete T lymphocyte colonies. Separation of these mononuclear cells on Sephadex G-10 columns yields enriched populations of T lymphocytes (greater than 95% E rosette-positive); these purified cells do not respond to this nonspecific mitogen by undergoing clonal expansion. Colony growth, however, can be restored by the addition of irradiated adherent cells. T cell responses can also be reconstituted by incubating the Sephadex-nonadherent fraction with irradiated cultured human tumor cells of monocytic (U937 and HL60) and B lymphocytic (Raji and Daudi cells) lines, but not from a T cell clone (MOLT-4) or erythroleukemic (K562) cells. Growth can also be induced in cultures containing T cells by adding cells from patients with either acute myeloblastic or B cell chronic lymphocytic leukemia or by the addition of B cell-enriched, monocyte-depleted normal mononuclear cells. Soluble factors prepared from Sephadex-adherent cells or active tumor cell lines are effective in promoting T cell colony formation. These results indicate that accessory cells are required for PHA responses of cloned human T cells. This function can be supplied by both monocytic and B lymphocytic tumor cell lines and is due to the release of soluble factors that act, in conjunction with the mitogen, to activate responsive lymphocytes.
Suppressor cell induction factor: a new mediator released by stimulated human lymphocytes and distinct from previously described lymphokines.
Authors: Kasakura S , Taguchi M , Watanabe Y , Okubo T , Murachi T , Uchino H , Hanaoka M 
Published: December 2022

Abstract
Suppressor cell induction factor (SIF) was produced by alloantigen-stimulated human peripheral blood lymphocytes, and it activated human T cells to become effective suppressors of the mixed lymphocyte reaction (MLR). The activity of SIF was resistant to 56 degrees C and to pH 2, and was precipitated by 50 to 80% saturated ammonium sulfate. SIF had a m.w. range, as determined by gel filtration, of 18,000 to 29,000; it did not bind to DEAE cellulose columns; and it was recovered in the pH range from 6.9 to 7.3 on isoelectric focusing. SIF was biochemically separable from IL 2, BF, IFN-gamma, and CSF. Furthermore, IL 2 activity was completely removed by absorption of MLC supernatants by murine cytotoxic T lymphocyte line (CTLL) cells, whereas SIF activity was unabsorbable, thus distinguishing SIF from IL 2. In addition, antiviral activity of MLC supernatants was completely abolished by anti-human IFN-gamma serum, whereas SIF activity was unaffected by this antiserum, thus distinguishing SIF from IFN-gamma. Since treatment of these supernatants with antiserum against human lymphoblastoid cell IFN(alpha/beta) had no effect on either antiviral or SIF activities in these supernatants, SIF was also distinguishable from IFN alpha/beta. These results indicate that SIF is a distinct new lymphokine with the ability to induce suppressor function in human T cells.