bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro anti-human immunodeficiency virus activities of tumor necrosis factor-alpha and interferon-gamma.
Authors: Wong G H , Krowka J F , Stites D P , Goeddel D V 
Published: December 2022

Abstract
Treatment of cells with tumor necrosis factor-alpha and interferon-gamma greatly reduces their susceptibility to infection with human immunodeficiency virus and suppresses the production of human immunodeficiency virus (HIV) mRNA, core protein p24, and infectious HIV. The combination treatment is cytotoxic for HIV-infected cells and reduces HIV RNA levels in chronically infected cells.
Qa-2 antigen encoded by Q7b is biochemically indistinguishable from Qa-2 expressed on the surface of C57BL/10 mouse spleen cells.
Authors: Sherman D H , Waneck G L , Flavell R A 
Published: December 2022

Abstract
Qa-2 was immunoprecipitated from the surface of 125I-labeled C57BL/10 (B10) mouse spleen cells and compared with Qa-2 immunoprecipitated from the surface of R1.1 thymoma cells transfected with Q7b. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that Qa-2 glycoproteins from both of these sources have a relative molecular mass of approximately 37 kDa. After treatment with endoglycosidase F, the Qa-2 polypeptide chains derived from C57BL/10 spleen and Q7b-transfected R1.1 cells displayed identical mobilities in sodium dodecyl sulfate-polyacrylamide gel electrophoresis because of removal of N-linked oligosaccharide residues. Furthermore, treatment of Qa-2 proteins from both sources with cyanogen bromide or alpha-chymotrypsin resulted in identical peptide fragmentation patterns. These results therefore provide a biochemical correlation between a cloned Qa-region gene produce expressed on the surface of transfected cells, and the Qa-2 glycoprotein on spleen cells that was described a decade ago by serologic methods.
Phorbol diesters and dioctanoylglycerol stimulate accumulation of both diacylglycerols and alkylacylglycerols in human neutrophils.
Authors: Rider L G , Dougherty R W , Niedel J E 
Published: December 2022

Abstract
Human neutrophils treated with phorbol 12-myristate 13-acetate (PMA) or dioctanoylglycerol exhibited a large (10-fold), sustained accumulation of the mass of diradylglycerol, beginning 1 min after stimulation and continuing for 30 to 60 min. Phorbol dibutyrate was less potent than PMA in stimulating diradylglycerol accumulation, whereas the 4-alpha analogs of PMA and phorbol dibutyrate were inactive. Submaximal concentrations of PMA (0.5 to 2.5 nM) plus the calcium ionophore, ionomycin (15 to 60 nM), led to synergistic accumulation of diradylglycerols. Chlorpromazine and sphingosine, inhibitors of protein kinase C, blocked PMA-stimulated accumulation of diradylglycerol with IC50 concentrations of 32 and 9 microM, respectively, paralleling their inhibition of PMA-stimulated O2- production. These compounds also inhibited the ionomycin-stimulated accumulation of diradylglycerols. A third protein kinase C inhibitor, H-7, was less effective, inhibiting PMA-stimulated accumulation of diradylglycerol by 25% at 100 microM. Differential sensitivity to alkaline hydrolysis suggests that diradylglycerols that accumulate in response to PMA or ionomycin stimulation are composed of a mixture of two distinct diglyceride species, diacylglycerols and alkylacylglycerols. Whereas diacylglycerol may activate cellular protein kinase C, the importance of the production of alkylacylglycerols is uncertain.
Potentiation of lymphokine-activated killer cell differentiation and lymphocyte proliferation by stimulation of protein kinase C or inhibition of adenylate cyclase.
Authors: Beckner S K , Farrar W L 
Published: December 2022

Abstract
Interleukin 2 (IL-2) stimulated the differentiation of human peripheral blood leukocytes into lymphokine-activated killer cells, as well as DNA synthesis of human T lymphocytes. Both effects of IL-2 could be inhibited by prostaglandin E2, a potent stimulator of adenylate cyclase; however, the inhibitory effect of prostaglandin E2 could be overcome by increased concentrations of IL-2. The opposite effects of IL-2 and prostaglandin E2 were paralleled by their respective abilities to inhibit and stimulate cAMP production in intact cells. Other agents, which inhibit adenylate cyclase directly (somatostatin, beta-endorphin, UK 14.3041) or indirectly by activation of protein kinase C (phenylephrine), could stimulate both differentiation and proliferation. None of these agents alone or in combination were as effective as maximal concentrations of IL-2. However, all agents potentiated differentiation and proliferation induced by submaximal and maximal concentrations of IL-2. Additionally, combinations of agents which stimulated protein kinase C with those that inhibited adenylate cyclase were additive in the potentiation of IL-2-induced differentiation. Neither inhibition nor potentiation of IL-2-induced lymphokine-activated killer cell differentiation was accompanied by changes in Tac expression or gamma-interferon production. The data indicate that the stimulation of lymphokine-activated killer cell differentiation and lymphocyte proliferation in human cells share a common initial biochemical signal. Although the inhibition of adenylate cyclase is not sufficient to maximally stimulate either process and cannot bypass the requirement for IL-2, modulation of this enzyme complex, positively or negatively, can regulate the ultimate physiologic response to IL-2.
Heart cross-reactive antigens of mutans streptococci share epitopes with group A streptococci and myosin.
Authors: Ayakawa G Y , Bleiweis A S , Crowley P J , Cunningham M W 
Published: December 2022

Abstract
Monoclonal antibodies (mAb) generated by immunization of mice with membranes of Streptococcus pyogenes Manfredo (M type 5) were tested for their reactivity with sodium dodecyl sulfate extracts of Streptococcus mutans GS5, Streptococcus rattus BHT (formerly S. mutans, serotype b), and S. mutans Ingbritt 175 in the Western blot. The reaction of the sodium dodecyl sulfate-extracted proteins of whole S. mutans, serotype b), and S. rattus with the mAb revealed that the shared cross-reactive antigens were near m.w. 62,000 to 67,000. Several higher m.w. proteins in S. mutans Ingbritt 175 reacted with the mAb but were not observed in the other two strains of streptococci. Cytoplasmic membranes of S. rattus BHT reacted with these mAb in the enzyme-linked immunosorbent assay and Western blot. The most reactive BHT membrane component detected by these mAb was a 62-kDa polypeptide that was similar in m.w. to the membrane component recognized by these antibodies in purified S. pyogenes membranes. The reactivity of the mAb with BHT membranes in the enzyme-linked immunosorbent assay was absorbed by rabbit skeletal muscle myosin. The patterns of reactivity observed in the BHT membrane immunoblots in this study closely resemble those previously obtained using polyclonal rabbit anti-human heart sera.
Inhibition of transformed T cell growth in vitro by monoclonal antibodies directed against distinct activating molecules.
Authors: Merćep M , Bluestone J A , Noguchi P D , Ashwell J D 
Published: December 2022

Abstract
Stimulatory of antigen-specific murine T cell hybridomas with the appropriate antigen has been shown to cause lymphokine secretion and inhibition of spontaneous cell growth. In this study, the effect of cellular activation on the growth of transformed T cells, of known or unknown antigen specificity, was explored with stimulatory monoclonal antibodies (mAb) that recognize nonclonally distributed T cell surface molecules. Anti-CD3 antibodies stimulated interleukin 2 (IL-2) secretion while they inhibited murine and human T cell tumor growth in vitro. Both responses required external cross-linking of the anti-CD3 antibodies. Activation via two molecules that are not physically associated with the T cell antigen receptor, Thy-1 and Ly-6, also inhibited transformed T cell growth while inducing IL-2 secretion. Notably, an anti-Thy-1 mAb that did not cause the transformed T cells to secrete lymphokines failed to affect their growth, and in fact blocked the growth inhibition induced by the stimulatory mAb. Regardless of which stimulating mAb was used, IL-2 production and cell growth were inversely proportional, manifesting similar antibody dose-response curves. Activation of a T cell hybridoma with stimulatory mAb resulted in rapid lysis, as evidenced by the release of 51Cr and lactate dehydrogenase. Cell cycle analysis demonstrated that cellular activation was accompanied by a cell cycle block between the G1 and S phases, and probably a slowing of the transit of cells already in S. These results demonstrate that the growth of a spectrum of neoplastic T cells, murine and human, can be inhibited by what are normally growth-promoting signals for non-transformed T cells.
Anti-interleukin 2 receptor antibody suppresses murine diabetic insulitis and lupus nephritis.
Authors: Kelley V E , Gaulton G N , Hattori M , Ikegami H , Eisenbarth G , Strom T B 
Published: December 2022

Abstract
In order to assess the importance of interleukin 2 receptor (IL-2R)-positive activated lymphocytes and macrophages in the pathogenesis of autoimmunity, we tested the prophylactic therapeutic efficacy of an anti-IL-2R (M7/20) monoclonal antibody, which recognizes the 55-kDa subunit of the heterodimeric IL-2R in two distinct models: the nonobese diabetic mouse and the NZB x NZW F1 hybrid with lupus. Treatment with anti-IL-2R monoclonal antibody suppressed autoimmune insulitis in nonobese diabetic mice and lupus nephritis in the NZB x NZW F1 hybrid. These studies indicate that highly selective targeting to activated lymphocytes and macrophages expressing the IL-2R provides a discrete method of dampening autoimmunity.
Human T cells can be directed to lyse tumor targets through the alternative activation/T11-E rosette receptor pathway.
Authors: Scott C F , Lambert J M , Kalish R S , Morimoto C , Schlossman S F 
Published: December 2022

Abstract
We investigated the ability of human T cells to be directed to lyse murine and human tumor targets by antibodies (Ab) to the T11-E rosette (CD2) receptor. We found that the human cytotoxic T lymphocyte clone TBI-6, which is specific for the Epstein-Barr virus-transformed cell line, CM-EBV, could be directed to lyse the Fc receptor-positive murine tumor P388D1, by the combination of anti-T11(2) plus anti-T11(3) Ab. This activation and lysis was demonstrable only with an Fc receptor expressing tumor target and only with those Ab or with anti-T3 (CD3) Ab but not with other anti-T11 Ab or other Ab directed against surface structures on the clone. We therefore constructed heterodimeric Ab consisting of anti-T11(2) or anti-T11(3) Ab and the J5 anti-common acute lymphoblastic leukemic antigen (anti-CALLA) Ab. The purity and retained functional properties of the dimers were demonstrated by sodium dodecyl sulfate-polyacrylamide gels, fluorescence-activated cell sorter analysis on relevant cells, and by the ability of these conjugates to activate human peripheral blood lymphocytes to proliferate. These heterodimeric Ab conjugates were shown to be able to direct the lysis of CALLA+ targets by TBI-6. The specificity of this lysis was demonstrated by the inability of these heterodimers to direct the lysis of CALLA- targets by the cytotoxic T lymphocyte clone, and by the ability of excess free J5, but not an irrelevant Ab of the same isotype, to block this type of lysis. The potential clinical significance of these reagents is discussed.
Antigen-driven differentiation of naive Ig-transgenic B cells in vitro.
Authors: Dustin L B , Bullock E D , Hamada Y , Azuma T , Loh D Y 
Published: December 2022

Abstract
We have established a culture system in which naive B cells bearing a transgenic, chicken OVA (cOVA)-specific Ig differentiate to plasma cells in vitro after interaction with cOVA plus cOVA-specific helper T cells. B cell-enriched populations from Ig-transgenic mice, but not from nontransgenic mice, proliferated after presenting nanomolar concentrations of cross-linked cOVA to DO11.10 (cOVA plus IAd-specific) T cells. After 6 to 9 days of culture with Ag and specific T cells, the B cells acquired a plasma cell phenotype and secreted the transgene-derived Ig at high levels. Engagement of B cell surface Ig was not essential for primary B cell differentiation. Differentiating B cells enlarged, clustered, and acquired two plasma cell markers, Syndecan and CD43. B cell CD45 isoform expression changed: the B220 isoform was lost in a T cell-dependent manner, whereas the CD45RB isoform was gained in a T-independent manner. Although unstimulated B cells survived less than 72 h in vitro, those in Ag-stimulated cultures showed reduced early death, a surge of proliferation at 3 to 5 days, and increased death late in the culture. Using a large population of naive B cells of defined antigenic specificity permits us to study a primary immune response to an Ag, rather than to less physiologic polyclonal stimuli. Because all steps of differentiation occurred in vitro, they are easily accessible for study. This coculture system provides an opportunity to observe Ag-specific T cell-B cell collaboration.
The CD40 ligand expressed by human B cells costimulates B cell responses.
Authors: Grammer A C , Bergman M C , Miura Y , Fujita K , Davis L S , Lipsky P E 
Published: December 2022

Abstract
The possibility that activated B cells might express a ligand for CD40 that was of functional importance for B cell responses was examined by using highly purified human peripheral blood B cells, as well as a variety of B lymphoblastoid cell lines and hybridomas. Following stimulation with the combination of a calcium ionophore and a phorbol ester, human B cells bound a soluble fusion protein containing the extracellular portion of CD40 and the Fc region of IgG1 (CD40.Ig). A variety of B cell lines and hybridomas also bound CD40.Ig, either constitutively or after activation. In addition, CD40.Ig specifically immunoprecipitated a 33-kDa glycoprotein from surface 125I-labeled activated B cells. The nucleotide sequence of the coding region of the CD40 ligand mRNA amplified by RT-PCR from activated T cells and B cell lines was identical. The CD40 ligand expressed on human B cells was important functionally because homotypic aggregation of CD40 ligand-expressing B cells was inhibited by the CD40.Ig construct. Additionally, RNA and DNA synthesis as well as Ig production by polyclonally activated, highly purified peripheral B cells and a variety of B cell lines were inhibited significantly by the CD40.Ig construct. Finally, B cell lines expressing the CD40 ligand induced Ig production from resting normal B cells in a CD40-dependent manner. These results indicate that human B cells express a ligand for CD40 that is identical with that expressed by activated T cells and that the B cell-expressed CD40 ligand plays an important role in facilitating responses of activated B cells.
Up-regulation of recombination activating gene expression by signal transduction through the surface Ig receptor.
Authors: Verkoczy L K , Stiernhdm B J , Berinstein N L 
Published: December 2022

Abstract
Recent evidence has demonstrated that a signal transduced through the lymphocyte Ag receptor may regulate the expression of the recombination activating genes (RAG). Although several groups have shown that such a signal may be required to down-regulate RAG-1 and RAG-2 after a functional Ag receptor has been generated in early mature T or B cells, recently it has been suggested that under some circumstances, cross-linking the B cell Ag receptor may result in up-regulation of RAG expression. To study this possibility, we used a unique set of cell variants isolated from a human mature B cell line, which differ in their expression of both the surface Ig receptor (sIg) and RAG-1 and RAG-2 genes. Two forms of stimulation were employed to generate a signal; either a soluble F(ab')2 anti-mu fragment or the combination of PMA and ionomycin. Northern blot analysis demonstrated that RAG-1 mRNA levels were increased in sIg+ variants after cross-linking with anti-mu. Increases were also observed in all variants after stimulation with PMA and ionomycin. Further analysis of cross-linked sIg+ variants suggests that the observed up-regulation in RAG expression was a reversible event. Furthermore, we have determined that both increased transcription and transcript stabilization contributed to this inducible up-regulation. We thus describe a mature B cell line in which RAG expression is up-regulated after sIg cross-linking. This finding is discussed in the context of its potential role in situations where sIg+ B cells may undergo secondary rearrangements for the purpose of "editing" their sIg receptors.
The role of c-Myb or a related factor in regulating the T cell receptor gamma gene enhancer.
Authors: Hsiang Y H , Goldman J P , Raulet D H 
Published: December 2022

Abstract
An enhancer has been localized 3 kb downstream of the C gamma 1 gene segment of the murine TCR-gamma locus. One element, the gamma 3 site, has been shown to be critical for its functional activity. Here we have determined that Myb-related transcription factors bind to the gamma 3 site and appear to be critical for the full activity of the TCR-gamma enhancer. c-myb products can transactivate the gamma 3 site in cell lines that do not ordinarily support enhancer activity of the gamma 3 site. Mutations in the myb site or an adjacent site for core-binding factor(s) prevent transactivation. c-myb expression in various cell lines is consistent with their capacity to activate the gamma 3 enhancer element using transient transfection assays. Therefore, c-Myb or a related factor appears to play an important role in regulating the murine TCR-gamma enhancer.
Cyclic AMP inhibits expression of the IL-2 gene through the nuclear factor of activated T cells (NF-AT) site, and transfection of NF-AT cDNAs abrogates the sensitivity of EL-4 cells to cyclic AMP.
Authors: Tsuruta L , Lee H J , Masuda E S , Koyano-Nakagawa N , Arai N , Arai K , Yokota T 
Published: December 2022

Abstract
cAMP inhibits PMA-induced IL-2 production at the transcriptional level in EL-4, a mouse lymphoma line. The region of the mouse IL-2 promoter covering positions from -321 to +46 relative to the transcription initiation site is required for activation by PMA and inhibition by cAMP. This region contains the nuclear factor of activated T cells (NF-AT), nuclear factor-kappa B (NF-kappa B), AP-1, and Oct binding sites, and the role of each element in responding to PMA and/or cAMP signals was characterized. The IL-2 promoter carrying mutations in each element reduced response to PMA while it retained sensitivity to cAMP, thereby suggesting that multiple elements contribute to positive and negative responses to PMA and cAMP, respectively. Using reporter plasmid carrying multiple copies of each element, we then found that the NF-AT construct was most effective in responding to PMA activation and to cAMP inhibition. Electrophoretic mobility shift assay revealed that, after exposure of cells to Bt2cAMP, NF-AT binding complex changed in amount or in mobility as a function of time. Furthermore, overexpression of the cytoplasmic component of NF-AT abrogated the inhibitory action of cAMP. These results indicate that the NF-AT site is a target of the inhibitory action of cAMP. In addition, binding of the NF-kappa B (p50/p65) heterodimer to the NF-kappa B site was inhibited by cAMP. Taken together, our data show that cAMP in EL-4 cells inhibits mouse IL-2 gene transcription through cis regulatory elements that include the NF-AT site as well as the NF-kappa B site.
Growth inhibition of Candida albicans hyphae by CD8+ lymphocytes.
Authors: Beno D W , Stöver A G , Mathews H L 
Published: December 2022

Abstract
We have shown previously that IL-2-activated splenocytes can inhibit the growth of Candida albicans hyphae in vitro. Herein we demonstrate that plastic nonadherent lymphocytes that are CD8+ mediate the antifungal activity. Enrichment for CD8+ cells markedly enhanced the antifungal activity of the IL-2-activated lymphocyte population for C. albicans and the cytotoxic activity of the lymphocytes for an NK-resistant cell line. Depletion of CD8+ cells reduced the lymphocyte population's antifungal activity and cytotoxic activity for the NK-resistant cell line. Enrichment for NK1.1+ cells markedly reduced the antifungal activity of the lymphocyte population for C. albicans and increased the cytotoxic activity of the lymphocytes for an NK-sensitive cell line. Depletion of NK1.1+ cells increased the lymphocyte population's antifungal activity and cytotoxic activity for the NK-resistant cell line. Generation of the antifungal lymphocytes in culture required IL-2 and was not replaced with IFN-gamma. These data show that IL-2-activated CD8+ T lymphocytes exert the greatest amount of antifungal effect against the hyphal form of C. albicans, whereas IL-2- or IFN-gamma-activated NK cells have little or no effect against the hyphae.
5-Fluorocytosine-induced eradication of murine adenocarcinomas engineered to express the cytosine deaminase suicide gene requires host immune competence and leaves an efficient memory.
Authors: Consalvo M , Mullen C A , Modesti A , Musiani P , Allione A , Cavallo F , Giovarelli M , Forni G 
Published: December 2022

Abstract
The nonmammalian cytosine deaminase (CD) enzyme converts the nontoxic prodrug 5-fluorocytosine (5-FC) to the toxic metabolite 5-fluorouracil. Parental cells of a mammary adenocarcinoma (TSA-pc) of BALB/c mice were transfected with the CD gene (TSA-CD), and the ability of 5-FC to hamper their growth was evaluated. A quantity amounting to 0.5 mg of 5-FC/0.3 ml of medium inhibits the proliferation of TSA-CD cells, but not that of TSA-pc, nor that of TSA-pc transfected with neomycin-resistance gene only (TSA-neo). In BALB/c mice, 800 mg 5-FC/kg of body weight injected daily i.p. for 30 days causes total regression of incipient (1-day-old), and established (3- and 7-day-old) TSA-CD tumors, and of 3-day-old experimental lung metastases, but does not impair TSA-pc nor TSA-neo cell growth. Because in CD8+ T lymphocyte- and granulocyte-depleted mice 5-FC no longer impairs TSA-CD growth, immune mechanisms appear to play an important role in this regression. Following, regression, all mice are resistant to subsequent s.c. or i.v. lethal challenges with TSA-pc. The induction of this immune memory is dependent on CD4+ lymphocytes, whereas its effector phase depends on both CD4+ and CD8+ lymphocytes. The memory elicited in tumor-bearing mice by the 5-FC-dependent regression of TSA-CD tumors cures a significant number of mice with 4-day-old TSA-pc metastases, but does not impair the growth of 4-day-old solid s.c. tumors. The reliability of this regression and the subsequent establishment of an efficient immune memory against poorly immunogenic TSA-pc offer the prospect that CD-transduced tumor cells and 5-FC can be used as components of a live antitumor vaccine.