bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of murine T cell proliferation by B cell stimulatory factor-1.
Authors: Grabstein K H , Park L S , Morrissey P J , Sassenfeld H , Price V , Urdal D L , Widmer M B 
Published: December 2022

Abstract
The proliferation of mitogen-activated primary T cells, antigen-activated memory T cells from mixed leukocyte culture, and antigen-dependent alloreactive T cell clones in response to purified murine recombinant B cell stimulatory factor-1 (also known as interleukin 4) was examined. We found that B cell stimulatory factor-1 (BSF-1) stimulated optimal proliferation of these T cells only after their recent activation by antigen or mitogen. Analysis of cell surface BSF-1 receptor expression indicated that although T cell activation is accompanied by a small increase in BSF-1 receptor expression, the cells also express BSF-1 receptors prior to activation at a time when they do not proliferate in response to BSF-1. BSF-1 was as effective a stimulus as interleukin 2 for inducing proliferation of the Lyt-2+ subpopulation of concanavalin A-activated murine spleen cells and an alloreactive cytolytic T cell clone. However, the L3T4+ subpopulation of concanavalin A-activated spleen and an alloreactive helper T cell clone were less responsive to BSF-1 than to interleukin 2. Taken together, the data indicate an important role for BSF-1 in the regulation of normal T cell proliferation.
Membrane-associated interleukin 1 is required for the activation of T cells in the anti-CD3 antibody-induced T cell response.
Authors: Hurme M 
Published: December 2022

Abstract
To establish the role of the membrane-associated form of IL 1 in T cell activation, we tested the accessory function of monocytes (Mo) that were unable to secrete or release soluble IL 1. The data obtained show that strictly purified resting T cells start to proliferate in response to anti-CD3 antibody (OKT3) stimulation in the presence of paraformaldehyde (PFA)-fixed Mo or 3-day cultured Mo (macrophages). The findings that i) PFA-fixed Mo did not produce or release IL 1, ii) the accessory function of PFA-fixed Mo could be inhibited with pretreatment with anti-IL 1 antibody, iii) PFA-fixed Mo had a comitogenic effect in the murine thymocyte assay, and iv) there was a temporal difference between the capacities to function in the comitogenic assay and to produce soluble IL 1, suggest that human Mo can express membrane-associated IL 1 and that it is functionally relevant.
Recombinant murine and human IL 1 alpha bind to human endothelial cells with an equal affinity, but have an unequal ability to induce endothelial cell adherence of lymphocytes.
Authors: Thieme T R , Hefeneider S H , Wagner C R , Burger D R 
Published: December 2022

Abstract
Consistent with the reports of others, we have demonstrated that human peripheral blood lymphocytes adhere to cultured human umbilical vein-derived endothelial cells (EC) in vitro. In our studies adherence was increased twofold to threefold by a 6-hr preincubation of the EC with IL 1. Recombinant human IL 1 alpha induced a maximal adherence response at less than 1 U per 2 X 10(4) EC. In contrast, recombinant murine IL 1 alpha was found to be 250- to 1250-fold less active in the adherence assay, based on units of IL 1 activity defined by the murine thymocyte proliferation assay. Moreover, when EC were preincubated with excess murine IL 1, no inhibition of the adherence-inducing effect of human IL 1 was noted. To characterize further this dichotomy of biological potency of murine and human IL 1 on the adherence assay, IL 1 binding studies were initiated. Recombinant human and murine IL 1 alpha were equally effective in inhibiting the binding of 125I-labeled human and murine IL 1, based on both micrograms of protein and units of IL 1 activity. The results of this study demonstrate that although human and murine IL 1 bind with equal affinity to receptors on human EC, human IL 1 is significantly more potent at inducing the increased EC adhesiveness for lymphocytes. The implications of these results for endothelial cell IL 1 receptor function are discussed.
Regulation of interleukin 2 synthesis by cAMP in human T cells.
Authors: Mary D , Aussel C , Ferrua B , Fehlmann M 
Published: December 2022

Abstract
T cell activation requires two initial signals that first lead to the expression of interleukin 2 (IL 2) receptors and the initiation of IL 2 synthesis and then to T cell proliferation. Jurkat T lymphoma cells have been shown to be a good model for studying IL 2 synthesis because these cells also require two signals for activation. The first signal can be provided by the lectin phytohaemagglutinin (PHA), and the second one by the phorbol ester, 12-o-tetradecanoylphorbol 13-acetate (TPA). The regulation of IL 2 synthesis in Jurkat cells, however, is unclear, and the present study deals with the role of cAMP on IL 2 synthesis. In Jurkat cells, IL 2 synthesis appears to be highly regulated by the activity of adenylate cyclase. This was demonstrated by using different means to increase intracellular cAMP level, namely by using permeant cAMP analogs, using the activator of adenylate cyclase, forskolin, using the activator of the alpha subunit of the stimulatory GTP binding protein cholera toxin, and using inhibitors of phosphodiesterase. In addition, prostaglandins E1 and E2 were shown to bind specifically to Jurkat cells, to induce a rise in intracellular cAMP level, and to markedly decrease IL 2 synthesis. All together, these results suggest that in T lymphocytes, the prostaglandin E2 receptor is linked to adenylate cyclase through a GTP binding protein and regulates the production of IL 2 by controlling the intracellular cAMP level.
A role for histamine type II (H-2) receptor binding in production of the lymphokine, soluble immune response suppressor (SIRS).
Authors: Schnaper H W , Aune T M , Roby R K 
Published: December 2022

Abstract
Soluble immune response suppressor (SIRS) is an immunosuppressive protein produced by human and murine suppressor cells activated by a variety of agents. Because histamine has been reported to activate suppressor cells, the possibility that it also induced SIRS production was investigated. Human lymphocytes treated with 10(-4) M histamine for less than 1 hr released a suppressive substance into culture supernatants that was physically, functionally and antigenically similar to human SIRS. Cimetidine and ranitidine, structurally distinct histamine type II (H-2) receptor antagonists, prevented histamine-induced SIRS production. In further experiments, suppression of human polyclonal IgM PFC responses by Con A and interferons, substances that activate the SIRS pathway, was inhibited by H-2 receptor antagonists. Activation of lymphocytes to produce SIRS by Con A or interferons was blocked by cimetidine or ranitidine. These data demonstrate that production of SIRS is induced by histamine, and raise the possibility that H-2 receptor binding may play a role in the SIRS pathway.
Rapid immune adherence reactivity of nascent, soluble antibody/DNA immune complexes in the circulation.
Authors: Edberg J C , Kujala G A , Taylor R P 
Published: December 2022

Abstract
Immune complex disease in humans and experimental animals can occur as a consequence of the binding of specific antibodies to exogenous or endogenous antigens. If this reaction occurs in the circulation, the fate of the resulting immune complex may depend upon many factors including the ability of the immune complex to fix complement and bind to complement receptors on circulating cells (immune adherence). We studied the in vivo formation and immune adherence of soluble antibody/dsDNA immune complexes in the circulation of both a nonprimate and a primate model. The fact that this sequence of biological recognition reactions is completed in less than 2 min suggests that the immune adherence phenomenon may play a crucial role in the clearance of nascent complement-fixing immune complexes from the circulation.
The stable and permanent expansion of functional T lymphocytes in athymic nude rats after a single injection of mature T cells.
Authors: Bell E B , Sparshott S M , Drayson M T , Ford W L 
Published: December 2022

Abstract
Athymic nude rats (PVG.rnu/rnu) were injected at 6 to 10 wk of age with 1 to 200 million thoracic duct lymphocytes (TDL) containing 40 to 60% mature T cells. Thereafter TDL-injected nude recipients were monitored for evidence of T cell function for up to 2 yr. W3/25+ T helper (Th) cells in lymph nodes (LN) increased from 7% at 2 wk to 30% at 8 wk after TDL transfer. The percent of W3/25+ cells remained elevated for the life of the recipient (up to 2 yr), approximating normal levels. The total size of the recirculating pool expanded in TDL-injected nude rats to reach 2/3 the level of euthymic controls by 16 wk, an increase of 10-fold to 15-fold in W3/25+ cells. The expansion of the W3/25+ population was independent of initial TDL dose. With time spleen and LN acquired a normal histological appearance including the development of germinal centres and a marked increase in cellularity in T cell traffic areas. TDL-injected nude rats rejected skin allografts with near normal kinetics. In addition graft vs host (GVH) responsiveness, assessed by the popliteal LN assay, progressively increased reaching a level 9 mo to 1 yr after replacement that resembled the GVH activity in euthymic controls.
Requirements for the simultaneous presence of phorbol esters and calcium ionophores in the expression of human T lymphocyte proliferation-related genes.
Authors: Kumagai N , Benedict S H , Mills G B , Gelfand E W 
Published: December 2022

Abstract
We have investigated the synergistic effects of phorbol ester and calcium ionophore on human T lymphocyte proliferation and the expression of the proliferation-related genes, c-myc, c-fos, interleukin 2 receptors (IL-2R) and interleukin 2 (IL-2). Incubation of T lymphocytes with both the phorbol ester, phorbol 12,13-dibutyrate (PDB), and the calcium ionophore, ionomycin, leads to the expression of a series of proliferation-related genes, followed by T cell proliferation. In contrast, stimulation of T cells sequentially with PDB and then ionomycin did not induce mitogenesis, demonstrating that simultaneous exposure to both agents is necessary for proliferation. Exposure of T cells to both agents together for different time periods resulted in a proliferative response in proportion to the duration of the exposure, with more than 6 hr required for maximum proliferation. In contrast, a 1-hr exposure to both drugs was sufficient for maximum expression of c-fos or c-myc proto-oncogene mRNA. The expression of IL-2R and the production of IL-2 were also dependent on the duration of simultaneous exposure to both phorbol ester and calcium ionophore. Levels of IL-2 mRNA became detectable at 1 hr and peaked at 3 hr after stimulation. The induction of IL-2 mRNA occurred only in the presence of both agents and became undetectable within 2 hr after the drugs were removed. In contrast, the expression of IL-2R mRNA became detectable at 1 hr, but was maintained even after the drugs were removed and reached a peak at 24 hr. Both IL-2 and IL-2R mRNA accumulated in proportion to the duration of the exposure. Augmentation of cell proliferation by exogenous IL-2 was observed in T cells exposed to the drugs for less than 3 hr. These data demonstrated that the induction of maximum expression of the nuclear proto-oncogenes c-myc and c-fos was not sufficient for PDB-ionomycin-induced T cell proliferation. The level of IL-2 mRNA accumulation and resultant IL-2 secretion is one of the limiting factors for proliferation of T cells exposed to the drugs for less than 3 hr, but not for longer exposures. Additional events such as accumulation of IL-2R mRNA and protein triggered by a long exposure to the drugs were obligatory for obtaining maximum proliferation.
Generation of lymphokine-activated killer cell activity from human thymocytes.
Authors: Ramsdell F J , Golub S H 
Published: December 2022

Abstract
We have generated lymphokine-activated killer (LAK) cells from human thymocytes in order to assess the relationship between LAK cells and T cells. Fresh thymocytes lack natural cytotoxic activity, and cytotoxicity cannot be stimulated by short term (1 hr) incubation with interferon or recombinant interleukin 2 (rIL-2). In addition, thymocytes are phenotypically devoid of cells bearing the natural killer (NK)-associated markers cluster designation (CD) 16 and NKH-1. After culture for 5 to 8 days with rIL-2, thymocytes display high levels of cytotoxic activity against both NK-sensitive and NK-resistant targets. Thymocytes require slightly more IL-2 than do peripheral blood lymphocytes to generate LAK activity. We have examined the phenotype of the thymocyte LAK precursor and effector cells. Thymocyte LAK precursors are of low to medium density, CD1-negative, and predominantly CD3-negative. Although CD3-positive cells proliferate in response to rIL-2, they are low in cytolytic capabilities. The effector cells, like the LAK precursors, are low to medium density lymphocytes. The cytotoxic cells are predominantly CD3-negative, and cytotoxic activity cannot be blocked with the use of anti-CD3 monoclonal antibodies. The effector cells also lack most NK-associated markers (HNK-1, and the CD16 markers Leu-11b and B73.1) but possess the NK-associated marker NKH-1 (N901). The responsive cell appears to be at a very early stage of thymic development, and it does not appear to either require or express the CD3-T cell receptor complex.
Haplotype-specific suppression of experimental allergic encephalomyelitis with anti-IA antibodies.
Authors: Sriram S , Topham D J , Carroll L 
Published: December 2022

Abstract
Treatment with monoclonal antibodies directed against the IA antigens of the MHC is known to alter the course and prevent a number of experimental autoimmune diseases. To determine whether the treatment in vivo with anti-IA antibodies is haplotype-specific, we studied the development of EAE in F1 (SJL/J X BALB/c) mice following anti-IA antibody therapy. We report that treatment of animals with monoclonal antibody directed against the high responder allele product, I-As, was successful in preventing disease when therapy was begun either at the time of immunization with antigen, or following passive transfer of MBP-sensitized T cells. Therapy with antibody directed to the low responder allele product (I-Ad), while effective when used at the time of immunization with antigen, was ineffective following passive transfer of MBP-sensitized lymphocytes.
Activation of human C1: analysis with Western blotting reveals slow self-activation.
Authors: Hosoi S , Circolo A , Borsos T 
Published: December 2022

Abstract
The first component of human complement was separated from C1-INH by sucrose linear gradient ultracentrifugation. Activation of C1 was studied in the absence and presence of immune complexes; activation was monitored by SDS-PAGE and Western blot. When the partially purified native C1 preparation was incubated at 37 degrees C without immune complexes, activated C1s appeared after 30 min in the case of eightfold dilution with respect to the original serum, and after 45 min with 32-fold dilution. Kinetics of appearance of activated C1r was the same as that of activated C1s. From the following results, we concluded that spontaneous activation may be partially due to proteolytic enzymes contaminating the preparation: 1) a nonspecific protease inhibitor, PMSF, completely inhibited spontaneous activation but did not inhibit the activation of C1 by immune complexes; 2) alpha 2-macroglobulin partially inhibited spontaneous activation, and 3) although spontaneous activation in the absence of PMSF was relatively slow, activated C1 accelerated spontaneous activation that was completely blocked by C1-INH. In contrast to spontaneous activation, the partially purified native C1 was rapidly activated by immune complexes: within 5 min almost all C1 was activated by rabbit IgG anti-human IgM-human IgM complexes. These results support conclusions derived from activation studies when using native C1 and hemolytic assays, and do not support those derived from the activation studies with reconstituted C1 and SDS-PAGE analysis. We suggest that the contradictions can be resolved if one assumes that C1 activation can be both an intra- and intermolecular process; which process dominates is determined by the state of C1 and by experimental conditions.
Lactoferrin effects of phagocytic cell function. II. The presence of iron is required for the lactoferrin molecule to stimulate intracellular killing by macrophages but not to enhance the uptake of particles and microorganisms.
Authors: Lima M F , Kierszenbaum F 
Published: December 2022

Abstract
Human lactoferrin (LF)--a neutrophil glycoprotein, the body fluid levels of which increase in inflammatory conditions--stimulates the phagocytic and cytotoxic properties of macrophages. We found in this work that, whereas the presence of iron in the LF molecule was not required to increase the capacity of mouse peritoneal macrophages (MPM) to take up Trypanosoma cruzi amastigotes (AMA), Listeria monocytogenes, or latex particles, it was necessary for LF to enhance intracellular killing of the two microorganisms. Thus, iron-free human lactoferrin (ApoLF), which did not increase MPM cytotoxicity, after restoration of ferric ions prior to its use in MPM treatments or when ferric citrate was added to the culture medium immediately after ApoLF treatment of the MPM, does increase MPM cytotoxicity. In that iron ions cannot be internalized as such, the latter observation suggested that ApoLF had taken up iron while membrane bound and then enhanced killing. Immunofluorescence studies revealed that comparable proportions of MPM-bound ApoLF or LF at either 20 or 100% iron saturation without appreciable differences in fluorescence intensity. Therefore, reduced binding of ApoLF compared with LF was not a likely explanation for the lack of effect of ApoLF on MPM killing. LF did not enhance AMA killing by MPM in the presence of the iron chelator deferoxamine. Diethylaminetriamine-pentaacetic acid, an iron chelator which is not incorporated into cells, had a similar effect. The iron-binding protein transferrin did not alter the capacity of MPM to either take up or kill the AMA, indicating that the noted LF effects were not shared by all iron-binding proteins. However, prior treatment of MPM with transferrin enabled the cells to display a greater parasite killing capacity after ApoLF treatment, suggesting a role for iron in this activity. Whether iron is required for LF to impart the signal that elicits enhanced killing, to satisfy a biochemical requirement for more effective killing, or both, remains to be clarified. We also found that killing of internalized AMA by LF-treated MPM--previously reported to be mediated in part by H2O2, O2-., and 1O2--was inhibitable by scavengers of OH., and therefore, appears to involve this oxygen metabolite as well.
Murine natural killer cells stimulated in vivo do not express the T cell receptor alpha, beta, gamma, T3 delta, or T3 epsilon genes.
Authors: Biron C A , van den Elsen P , Tutt M M , Medveczky P , Kumar V , Terhorst C 
Published: December 2022

Abstract
Murine blast natural killer (NK) cells responding to in vivo stimulation were isolated and characterized as to their expression of the T cell receptor (TCR) variable genes alpha, beta, and gamma and the TCR constant genes T3 delta and T3 epsilon. In vivo stimulated blast T cells were isolated for comparison. RNA extracted from highly purified blast cell populations elicited in vivo was probed for TCR transcripts by Northern blot analysis. In contrast to the blast T cells which expressed high levels of the alpha, beta, delta, and epsilon genes, blast NK cells expressed very low to not detectable levels of these genes. Blast NK cells isolated from euthymic mice were comparable to those isolated from athymic mice and both populations had profoundly reduced levels of transcripts for TCR genes. The expression of gamma-chain genes was extremely low in the in vivo elicited blast T cells as well as the blast NK cells. Highly purified NK cells isolated from unmanipulated mice and propagated in culture with recombinant interleukin 2 for short periods of time also had extremely low levels of delta and epsilon, whereas T cells expanded in culture had high level expression of these genes. As delta and epsilon appear to be required for expression of a functional recognition structure on the T cell surface and are expressed early in T cell ontogeny, these results indicate that the functional NK cells responding to proliferation signals do not form a conventional T cell recognition structure. Furthermore, the results support a separation of the T cell and NK cell lineages early in ontogeny.
Unusual immunoglobulin DNA sequences from the nonexpressed chromosome of mouse normal B lymphocytes: implications for allelic exclusion and the DNA rearrangement process.
Authors: Nottenburg C , St John T , Weissman I L 
Published: December 2022

Abstract
Allelic exclusion of immunoglobulin gene products results in the expression of only one of two possible alleles in normal B lineage cells. Attempts to define the role of heavy chain gene rearrangements in this process have revealed the nonexpressed allele to be rarely in its germline context, but rather incompletely rearranged (D/J rearrangements) or completely rearranged (V/D/J rearrangements) and in a context that cannot be expressed as a protein. Nearly all DNA sequences of heavy chain genes from the nonexpressed allele have originated from plasmacytomas, virus-induced pre-B leukemias, and hybridomas--all clonal cell lines perhaps altered by the neoplastic process. In this communication, we present the first examples of isolation and DNA sequence analysis of heavy chain gene rearrangements from the nonexpressed allele of normal B lymphocytes. Splenic B lymphocytes from allotype heterozygous (BALB/c X C57BL/6J)F1 mice expressing the BALB/c IgD allotype were detected with a monoclonal antibody, H10-4.22, to the BALB/c delta chain genetic marker and were isolated with a FACS (fluorescence-activated cell sorter). lambda phage clones containing the JH gene region from the sorted cells were isolated, and those containing sequences derived from the C57BL/6J nonexpressed chromosome were identified by a restriction fragment length polymorphism. DNA sequences of seven rearranged clones from the nonexpressed allele are presented. Five of these rearrangements have unexpected compositions. Four of the five clones contain V/D/J rearrangements with no obvious impediments to expression generated by the rearrangements. The novel variable region gene in one of these V/D/J rearrangements is a member of a newly described VH gene family. The fifth clone has a 3.5 kb deletion removing all of the JH gene segments. The remaining two clones contain D/J rearrangements that are typical of the initial stage of variable region assembly. These findings suggest that the mechanisms that generate nontranslatable heavy chains do not exclusively account for allelic exclusion. Rather, several different mechanisms may contribute to the establishment of allelic exclusion in normal B lymphocytes.