bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low doses of IL-4 injected perilymphatically in tumor-bearing mice inhibit the growth of poorly and apparently nonimmunogenic tumors and induce a tumor-specific immune memory.
Authors: Bosco M , Giovarelli M , Forni M , Modesti A , Scarpa S , Masuelli L , Forni G 
Published: December 2022

Abstract
The ability of rIL-4 to trigger host reactivity against both a chemically induced fibrosarcoma (CE-2) and a spontaneous adenocarcinoma (TS/A) of BALB/c mice was studied. Daily local s.c. administration around tumor draining lymph nodes of 10 injections of progressive amounts (0.00001 to 1000 pg/day) of rIL-4 induced appreciable inhibition of the growth of both tumors after a dose-response survival curve peaking at 0.1 pg/day. Inasmuch as rIL-4 has no direct antitumor activity, as shown by in vitro tests, host immune reactivity plays a fundamental role in this lymphokine activated tumor inhibition (LATI). LATI, in fact, is abolished when recipient mice are sublethally irradiated or treated with cyclosporin A, or when the reactivity of CD4+ lymphocytes is suppressed, whereas it is not affected by anti-asialo GM1 antibody. The morphologic data show that rIL-4 LATI rests on the recruitment of several cell reaction mechanisms, among which those that are nonspecific seem to predominate. rIL-4 LATI also leads to a state of long lasting and specific immune memory: the growth of a second contralateral tumor challenge is significantly impaired after LATI. This immune memory takes place after LATI of both the poorly immunogenic CE-2 fibrosarcoma and the TS/A adenocarcinoma, previously classed as nonimmunogenic on the basis of immunization-protection tests. In the latter case, adoptive transfer experiments show that Thy-1+ lymphocytes and, in particular, the CD4 cell-depleted T lymphocyte subpopulation, are responsible for the immune memory. Finally, the ability of rIL-4 to trigger LATI is greater than that of the most effective doses of rIL-2, rIL-1 beta, and IFN-gamma, whereas its association with rIL-1 beta induces a more effective immune memory.
IL-7 induces human lymphokine-activated killer cell activity and is regulated by IL-4.
Authors: Stötter H , Custer M C , Bolton E S , Guedez L , Lotze M T 
Published: December 2022

Abstract
Induction of lymphokine-activated killer (LAK) activity by IL-2 has been described and characterized as broadly cytolytic activity against both fresh and cultured tumors. rIL-7 in the absence of IL-2 also induces LAK activity in human cells. This activity is unique for IL-7, because it is not shared by other cytokines including IL-1, IL-4, IL-6, and TNF-alpha. IL-7 also induces either de novo or increased expression of the surface markers CD25 (Tac, IL-2R alpha-chain), CD54 (ICAM-1), Mic beta 1 (IL-2R beta-chain) and CD69 (early T cell activation Ag). IL-7-induced LAK activity is independent of IL-2 secretion, because it is not abrogated by IL-2 antisera. The LAK precursor responding to IL-7 stimulation is enriched in the null cell fraction as has been demonstrated for IL-2-induced LAK cells. TGF-beta and IL-4 interfere with generation of LAK activity by IL-7. Anti-IL-4 antiserum enhances IL-7-induced LAK activity and augments induction of surface marker expression by IL-7. This may be indirect evidence that IL-7 stimulation leads to induction of IL-4 activity. Our results describe the activation of mature lymphoid cells by IL-7. This and the previously described role of IL-7 in lymphohemopoiesis makes it a cytokine of potential therapeutic value for treatment of immunodeficiency states and possibly the immunotherapy of cancer.
Transfectomas expressing both secreted and membrane-bound forms of chimeric IgE with anti-viral specificity.
Authors: Sun L K , Liou R S , Sun N C , Gossett L A , Sun C , Davis F M , MacGlashan D W , Chang T W 
Published: December 2022

Abstract
Because of the lack of a cell line expressing on surface and secreting human IgE of known Ag specificity, the construction of a transfectoma line possessing such properties would be useful for studying the roles of surface IgE and the effects of anti-IgE antibodies on IgE-producing B cells. Toward this goal, the human genomic DNA segment encompassing the two exons encoding the membrane anchor peptide of epsilon-chain and their flanking regions was sequenced. Hybrid epsilon and kappa genomic DNA comprising the C regions of human epsilon- and kappa-chains and the H and L chain V regions of the murine mAb BAT123, which reacts with the gp120 envelope protein of HIV-1, were constructed. Mammalian expression vectors containing these fusion genes were used to transfect murine myeloma Sp2/0 cells, and transfectants stably expressing on surface and secreting into culture medium chimeric IgE were obtained. The chimeric IgE showed identical Ag-binding properties as the murine mAb BAT123. Acting in concert with the specific peptide Ag polyvalently coupled to a protein carrier, the chimeric antibody could induce histamine release from human blood basophils. These results demonstrate the potential utility of the transfectoma cells and the chimeric IgE in studying the roles of membrane-bound IgE and effects of anti-IgE antibodies on IgE-producing B cells.
The expression of IL-2R alpha-chain is enhanced by activation of adenylate cyclase in large granular lymphocytes and natural killer cells.
Authors: Koyasu S , Tagaya Y , Sugie K , Yonehara S , Yodoi J , Yahara I 
Published: December 2022

Abstract
An increase in intracellular cAMP level induced the expression of IL-2R alpha-chain, the 55-kDa component of IL-2R complex, in a human NK-like cell line, YT. We show here that forskolin also induces the expression of IL-2R alpha-chain on mouse large granular lymphocytes (LGL) but not on T cells. In contrast, treatment with a combination of phorbol ester and calcium ionophore, which is a strong inducer of IL-2R alpha-chain on T cells, does not induce the expression of the alpha-chain on LGL cells. Forskolin was shown to activate the transcription of IL-2R alpha-chain gene in YT cells as revealed by the chloramphenicol acetyltransferase assay. Chemical cross-linking experiments using radio-iodinated IL-2 also supported the enhanced expression of IL-2R alpha-chain by treatment with forskolin. In contrast to the alpha-chain, IL-2R beta-chain was not induced by forskolin as revealed by flow cytofluorometry with a mAb against the beta-chain molecule. These results indicate that the activation of adenylate cyclase induces or/and enhance the expression of IL-2R alpha-chain at the transcriptional level in LGL/NK cells including mouse LGL and human YT cell, which leads to the enhanced expression of high affinity IL-2 receptors.
Production of prostaglandin E2 and prostacyclin by thymic nurse cells in culture.
Authors: McCormack J E , Kappler J , Marrack P , Westcott J Y 
Published: December 2022

Abstract
To better define the thymic microenvironment, we have examined a specific population of thymic stromal cells, thymic nurse cells (TNC) for production of eicosanoids. TNC were prepared from BALB/c mice, cultured in complete medium, and culture supernatants were analyzed for the presence of various metabolites of arachidonic acid. Freshly isolated TNC produced large quantities of PGE2 and 6-keto PGF1 alpha (a stable metabolite of prostacyclin, PGI2). Both of these eicosanoids were produced continuously in culture, after an initial lag period of approximately 2 h. No significant production of the eicosanoids PGD2, thromboxane B2, or leukotrienes B4, C4/D4/E4 was seen in these cultures. Production of PGE2 and PGI2 by TNC was not stimulated by treatment with the calcium ionophore A23187, or by cell-cell interactions resulting from coculture of the TNC with free thymocytes. Eicosanoid production in these cultures was not due to production of these substances by cells likely to be present as contaminants, such as T rosettes or free thymocytes. These findings raise the possibility that PGE2 and/or PGI2 may provide signals to thymocytes at a specific developmental stage.
Deficiency in early development of the thymus-dependent cells in irradiation chimeras attributable to recipient's environment.
Authors: Iwabuchi C , Iwabuchi K , Kobayashi S , Ogasawara K , Negishi I , Wang B Y , Wambua P P , Arase H , Fukushi N , Itoh Y 
Published: December 2022

Abstract
Allogeneic bone marrow chimeras were prepared using reciprocal combinations of AKR and C3H mice. When C3H mice were recipients, the number of thymocytes recoverable from such chimeras (C3H recipient chimeras) was small as compared with that from chimeras for which AKR mice were used as recipients (AKR recipient chimeras) regardless of donor strain. The thymocytes from C3H recipient chimeras showed a profound deficiency in generating proliferative responses to stimulation by anti-CD3 mAb (2C11) or anti-TCR (alpha, beta) mAb (H57-597), even though the expression of CD3 and TCR molecules fell within the same range as that in AKR recipient chimeras. Furthermore, after stimulation with immobilized 2C11, the proportion of IL-2R+ cells in the thymocytes from C3H recipient chimeras was much less than that in AKR recipient chimeras. However, no significant difference in proliferative responses to 2C11 plus PMA, in influx of Ca2+ after stimulation with 2C11 or IL-2 production in response to 2C11 plus PMA or PMA plus A23187 was demonstrated between C3H and AKR recipient chimeras. These findings suggest that the thymocytes from C3H recipient chimeras have a deficiency in the signal transduction system as compared with chimeras for which AKR mice are the recipients. The thymic stromal component involved in this difference in the C3H recipient chimeras is discussed.
Enhanced HIV replication in macrophage colony-stimulating factor-treated monocytes.
Authors: Kalter D C , Nakamura M , Turpin J A , Baca L M , Hoover D L , Dieffenbach C , Ralph P , Gendelman H E , Meltzer M S 
Published: December 2022

Abstract
Monocytes cultured 7 to 10 days in recombinant human macrophage CSF (MCSF) were greater than 400-fold more susceptible to HIV infection than an equal number of cells cultured in medium alone. Levels of reverse transcriptase activity and p24 Ag in culture fluids of monocytes treated with MCSF 1 wk before and continuously after HIV infection were significantly greater than those of control cells cultured without MCSF. HIV-induced cytopathic effects in the MCSF-treated cultures also increased in both frequency and extent. At any given viral inoculum, the frequency of HIV-infected cells, the level of HIV mRNA/infected cell, and the level of proviral DNA/infected culture in MCSF-treated monocyte cultures were dramatically greater than those in control cultures. These differences were directly related to MCSF concentration to a maximum between 750 and 1000 U/ml MCSF, and were evident at all time points examined through 5 wk. None of the preceding effects was observed when MCSF was added at the time of or 1 wk after HIV infection. These data suggest that the predominant effect of MCSF for control of HIV infection is on the monocyte itself, not the virus. If these in vitro observations extend to the HIV-infected patient, then the variable levels of MCSF in tissue or blood may determine both the susceptibility of macrophages to virus infection and the extent of virus replication in infected cells.
Inhibition of multicycle influenza virus replication by hybrid antibody-directed cytotoxic T lymphocyte lysis.
Authors: Moran T M , Usuba O , Kuzu H , Kuzu Y , Schulman J , Bona C A 
Published: December 2022

Abstract
Bifunctional antibodies with specificity for the TCR/CD3 complex as well as to a target cell-surface Ag can redirect CTL to lyse the target cell. We have produced a hybrid hybridoma, HHA6, which secretes bifunctional antibodies capable of redirecting CTL to lyse influenza virus-infected target cells. When added along with CTL to virus-infected cells, these antibodies very efficiently inhibit multicycle virus replication. Because hybrid hybridomas reassort H and L chains randomly we attempted to purify bifunctional antibody by using HPLC. The purification increased the potency of HHA6. This increase probably reflects an enrichment of the active species and the removal of inhibiting antibody species.
Suppression of human monocyte function against Candida albicans by autologous IL-2-induced lymphokine-activated killer cells.
Authors: Wei S , Serbousek D , McMillen S , Blanchard D K , Djeu J Y 
Published: December 2022

Abstract
We have previously reported that IL-2-induced lymphokine-activated killer (LAK) cells have the capacity to lyse autologous and allogeneic monocytes. To understand the biologic significance of this interaction, we investigated the function of human monocytes against the opportunistic pathogen, Candida albicans, subsequent to a short exposure to autologous LAK cells. A highly sensitive radiolabel assay, which makes use of the incorporation of [3H]glucose into residual Candida after their incubation with monocytes, was developed to measure antifungal activity. Cultured monocytes, after 2 to 6 h exposure to LAK cells, were found to be substantially suppressed in their ability to control fungal growth. Moreover, monocytes cultured in the presence of granulocyte/macrophage (GM)-CSF or IL-3, were even more suppressed in function after a short incubation with LAK cells. The effect of GM-CSF was both time and dose dependent, with peak susceptibility induced after 4 days of culture with as little as 10 U/ml of the cytokine. These GM-CSF-cultured monocytes, however, were relatively resistant to inhibition by freshly isolated large granular lymphocytic NK cells. Therefore, IL-2 induces in large granular lymphocytic cells the capacity to inhibit monocyte function. In contrast to GM-CSF and IL-3, IFN-gamma was found to have a protective effect on monocytes, because monocytes cultured 4 days in IFN-gamma were not significantly inhibited by LAK cells. These results indicate that LAK cells may be involved in regulation of monocyte function and suggest that the state of differentiation induced by different cytokines may dictate the level of control of the monocytes by LAK cells.
Complete cDNA sequence of human complement pro-C5. Evidence of truncated transcripts derived from a single copy gene.
Authors: Haviland D L , Haviland J C , Fleischer D T , Hunt A , Wetsel R A 
Published: December 2022

Abstract
Two truncated human C5 clones, pHC5A and pHC5B, were isolated from an adult human liver cDNA library, and contained inserts of 2930 and 2181 bp, respectively. Both clones were polyadenylated and encoded the 5'-end of the C5 pro-molecule, thereby completing the human pro-C5 cDNA sequence. However, near the 3'-ends, at exon/intron boundaries, the nucleotide sequences of pHC5A and pHC5B diverged from each other and from the full-length 6.0-kb C5 cDNA sequence. Clone pHC5A, which overlapped the first human C5 clone described (J-16), encoded most of the C5 signal peptide, the complete beta-chain, the linker peptide, 177 amino acids of the alpha-chain, and contained 144 bp of Alu family consensus sequence encoding 48 amino acids of divergent protein sequence in an open reading frame. Clone pHC5B encoded the entire C5 signal peptide, the beta-chain, the linker peptide, nine amino acids of the alpha-chain, and six amino acids of divergent protein sequence in an open reading frame. Northern blot experiments demonstrated the presence of a 3.0-kb truncated C5 mRNA in adult human liver and a 4.8-kb truncated C5 mRNA in HepG2 cells in addition to the 6.0-kb full-length transcript. Truncated C5 mRNA were not detected in Raji, MOLT-4, human fibroblast or U937 cells, although the full-length 6.0-kb transcript was seen in MOLT-4 cells. Southern blot analyses indicated that the human C5 structural gene is large, complex, and is present in the human genome in a single copy, thereby demonstrating that the truncated C5 clones and mRNA are derived from a single C5 gene by alternative processing events.
Induction of NF-KB during monocyte differentiation by HIV type 1 infection.
Authors: Suzan M , Salaun D , Neuveut C , Spire B , Hirsch I , Le Bouteiller P , Querat G , Sire J 
Published: December 2022

Abstract
The production of human immunodeficiency virus type 1 (HIV-1) progeny was followed in the U937 promonocytic cell line after stimulation either with retinoic acid or PMA, and in purified human monocytes and macrophages. Electrophoretic mobility shift assays and Southwestern blotting experiments were used to detect the binding of cellular transactivation factor NF-KB to the double repeat-KB enhancer sequence located in the long terminal repeat. PMA treatment, and not retinoic acid treatment of the U937 cells acts in inducing NF-KB expression in the nuclei. In nuclear extracts from monocytes or macrophages, induction of NF-KB occurred only if the cells were previously infected with HIV-1. When U937 cells were infected with HIV-1, no induction of NF-KB factor was detected, whereas high level of progeny virions was produced, suggesting that this factor was not required for viral replication. These results indicate that in monocytic cell lineage, HIV-1 could mimic some differentiation/activation stimuli allowing nuclear NF-KB expression.
Analysis of MHC class I gene expression in adult bone marrow and fetal liver of the BALB/c mouse.
Authors: Cheroutre H , Kronenberg M , Brorson K , Hunt S W , Eghtesady P , Hood L , Nickerson D A 
Published: December 2022

Abstract
The BALB/c mouse has at least 29 class I genes encoded in the Qa, Tla, and Hmt (histocompatibility dependent on a maternally transmitted factor) regions of the MHC. The pattern of expression of these class Ib MHC genes is not well characterized, although some of their products such as the serologically detectable Qa-2 and TL Ag are expressed mainly in lymphoid and hematopoietic tissues. In this study, the expression pattern of BALB/c class I genes has been analyzed in adult bone marrow and fetal liver. cDNA libraries were synthesized from these tissues, and isolated class I cDNA clones were characterized by hybridization with oligonucleotide probes and by nucleotide sequence analysis. Of the 29 total class Ib genes, transcripts of five including Q6d, Q7d, T9c, T10c, and the 37 gene were isolated from the bone marrow cDNA library. Four of these can encode proteins; the sequence of the T10c gene demonstrates it is most likely a pseudogene. A non-overlapping set of three class Ib cDNA clones was obtained from the fetal liver, including T13c, the Thy 19.4 gene, and a previously uncharacterized class I gene provisionally designated as FL 57.2. Although the majority of H-2Dd cDNA clones that were analyzed lack introns, many of the class Ib cDNA clones contain intron sequences. This suggests that the expression of some of these genes may be regulated at the level of RNA splicing. The T13c gene encodes the thymus leukemia Ag in BALB/c mice. We have confirmed that the T13c gene is expressed in fetal liver by flow cytometric analysis of cells stained with anti-TL mAb.
Stimulation of B lymphocytes through surface Ig receptors induces LFA-1 and ICAM-1-dependent adhesion.
Authors: Dang L H , Rock K L 
Published: December 2022

Abstract
Engagement of the surface Ig receptor with anti-IgM antibodies stimulates murine B lymphocytes to markedly increase their expression of the cell adhesion molecules ICAM-1 and LFA-1. Stimulated B cells display increased homotypic adhesiveness and form spontaneous heterotypic conjugates with T lymphocytes. This latter T-B cell interaction is further enhanced if T cells have been previously activated with phorbol esters. In all cases, the formation of cell-cell conjugates is dependent on LFA-1-ICAM-1-mediated interactions as assessed in mAb blocking experiments. B lymphocytes stimulated with anti-IgM display a marked increase in binding to ICAM-1-transfected L cells. This cell-cell interaction is inhibited by anti-LFA-1 mAb binding to the B lymphocyte. Together, these results demonstrate that there is an induction of both ICAM-1 and LFA-1 on stimulated B cells and a corresponding increase in the adhesiveness of these cells. These findings suggest that Ag binding to the surface Ig receptor could prepare a B lymphocyte for subsequent interaction with a T lymphocyte. This provides insight into how efficient T-B collaboration may occur between very infrequent Ag-specific lymphocytes.
Regulation of lymphokine-activated killer activity and pore-forming protein gene expression in human peripheral blood CD8+ T lymphocytes. Inhibition by transforming growth factor-beta.
Authors: Smyth M J , Strobl S L , Young H A , Ortaldo J R , Ochoa A C 
Published: December 2022

Abstract
The effect of transforming growth factor-beta 1 (TGF-beta) on activation-induced CD8+ T cell cytotoxicity and gene expression was investigated. TGF-beta was demonstrated to inhibit pore-forming protein (PFP) mRNA expression and total benzoyloxycarbonyl-L-lysine thiobenzyl ester esterase activity in CD8+ T cells cultured with IL-2 and OKT3 mAb for 6 to 18 days. Consistently, in the absence or presence of TGF-beta, the PFP mRNA expression and lymphokine-activated killer (LAK) activity of CD8+ T cells were closely correlated. The inhibitory effects of TGF-beta on both CD8+ T cell PFP mRNA expression and LAK activity were reversible by removal of TGF-beta from the culture. Expression of lymphokines, adhesion/recognition molecules, and activated p55 IL-2R, previously implicated in the lytic mechanism of cytotoxic lymphocytes, either was not detectable or did not correlate with TGF-beta inhibition of LAK activity. In addition, independently of effector/target cell binding, the lectin- or heteroconjugated antibody-dependent cellular cytotoxicity of IL-2/OKT3 mAb-activated CD8+ T cells was inhibited by preculture with TGF-beta. TGF-beta also inhibited the rapid activation-induced expression of PFP mRNA and cytotoxic potential in resting T cells, thereby indicating that the effect of TGF-beta was independent of T cell proliferation. TGF-beta inhibition of CD8+ T cell PFP mRNA expression and cytotoxic potential was TGF-beta dose dependent; however, a variety of activation stimuli (including IL-2, IL-6, and OKT3 mAb) were all similarly inhibited by TGF-beta. Therefore, TGF-beta may be an important general regulator of CD8+ T cell cytotoxic function, in particular by suppressing expression of PFP, a major cytolytic protein implicated in the lytic function of cytotoxic lymphocytes.