bluuebunny/crossref_metadata_2025_split huggingface dataset:
Requirement for three distinct lymphokines for the induction of cytotoxic T lymphocytes from thymocytes.
Authors: Takai Y , Herrmann S H , Greenstein J L , Spitalny G L , Burakoff S J 
Published: December 2022

Abstract
The induction of cytotoxic T lymphocytes (CTL) from CTL precursors requires a combination of antigen and lymphokine signals. To investigate lymphokine requirements for CTL generation, we used an assay in which helper T cell and accessory cell-depleted spleen cells or whole thymocytes were cultured with lectin (Con A) and lymphokines. This culture was followed by assessment of lectin-dependent cytolysis. High concentrations of recombinant interleukin 2 (R-IL 2) (100 U/ml) alone were not sufficient for lectin-mediated CTL induction from thymocytes, whereas 20 to 100 U/ml of R-IL 2 alone could induce a significant lectin-mediated CTL response from accessory cell-depleted spleen cells. Using thymocytes as responders, we found purified or recombinant interferon-gamma (IFN-gamma) did not cause cytolytic activity either in the absence of or in the presence of R-IL 2. However, supernatant from Con A-stimulated rat spleen cells (rat Con A SN) in combination with R-IL 2 could induce cytolytic activity, suggesting that several factors are required for CTL induction. Con A SN was fractionated by gel filtration and the fractions were tested for ability to induce CTL. In the presence of a low level of R-IL 2 (5 U/ml), fractions with a Mr of approximately 31,000 could induce CTL, and this activity was referred to as CTL differentiation factor (CDF). The peak fractions containing CDF activity did not have detectable IL 1, IL 2, IFN-gamma, or CSF activity. However, by add-back experiments and the use of blocking antibodies, a monoclonal antibody against the IL 2 receptor or antibodies against murine IFN-gamma, we demonstrated that CTL induction from mature thymocytes (L3T4-, Lyt-2+) requires CDF activity in addition to IL 2 and IFN-gamma.
The interleukin 2 secretion defect in vitro in systemic lupus erythematosus is reversible in rested cultured T cells.
Authors: Huang Y P , Miescher P A , Zubler R H 
Published: December 2022

Abstract
Interleukin 2 (IL 2) secretion in response to mitogenic stimulation in vitro is strongly reduced in circulating T lymphocytes from patients with SLE. It is still not clear how this abnormality relates to the B cell hyperactivity in the disease. Some investigators proposed that an intrinsic T helper cell defect could lead to suppressor cell dysfunction and autoimmunity. Others have found that in fact increased suppressor cell activity can cause IL 2 hyposecretion. In the present study we report that the IL 2 secretion in response to PHA plus PMA by T cells from patients with SLE, which initially was decreased by a factor of 10 as compared with the IL 2 secretion in blood donor T cells, was restored when the T cells were rested for 2 to 3 days in culture before stimulation. IL 2 hyposecretion in SLE T cells and the kinetics of normalization in culture were not changed by the addition of normal adherent cells during the stimulation with PHA/PMA, occurred in the absence of significant cell death or proliferation or change of the T4:T8 cell ratio during the resting culture, were not due to a maturation of immature T6-positive cells (less than 1.5% T6 cells in SLE T cells), and also occurred in T8-depleted T4 cells alone. Furthermore, a normalization of IL 2 secretion took place in the presence of either SLE serum or normal serum, and the addition of fresh autologous T cells to 3-day-cultured SLE T cells did not cause suppression of IL 2 secretion. These data show that some rapidly reversible defect occurs in circulating T helper cells in SLE. That this could reflect an exhaustion of T helper cells that have been activated in vivo is discussed.
Human basophil releasability. III. Genetic control of human basophil releasability.
Authors: Marone G , Poto S , Celestino D , Bonini S 
Published: December 2022

Abstract
Basophil releasability implies that, in addition to the surface density of IgE molecules, biochemical events determine the capacity to release chemical mediators in response to activating stimuli. We studied the IgE (anti-IgE)-mediated and non-IgE-mediated (f-met peptide and the Ca2+ ionophore A23187) releasability of human basophils obtained from 14 monozygotic (MZ) (ages 25.7 +/- 13.3 yr; mean +/- SDM) and 13 dizygotic (DZ) twin pairs (ages 20.4 +/- 9.9 yr). A significant intrapair correlation coefficient of the maximal percent of anti-IgE-induced histamine release was found in the MZ, whereas no significant correlation was found in the DZ. The mean intrapair variance of anti-IgE-induced histamine release in MZ (VMZ) and in DZ (VDZ) gave an F value equal to 3.84 (p less than 0.01) and a heritability (H) index of 0.74. Similar findings were obtained with respect to the sensitivity to a standard concentration (10(-1) micrograms/ml) of anti-IgE. No correlation between serum IgE level and anti-IgE-induced histamine release was found in either MZ or DZ. A significant intrapair correlation coefficient of f-met peptide-induced histamine release was found in both the MZ and the DZ. The difference between MZ and DZ was not significant. The VMZ and the VDZ of the f-met peptide-induced histamine release gave an F value of 1.52 (NS) and an H value of 0.34. The intrapair correlation coefficient of A23187-induced release was significant in MZ and not significant in DZ. The mean intrapair variance of A23187-induced histamine release gave an F value of 2.33 (NS) and an H index of 0.57. Similar findings were obtained by using suboptimal (3 X 10(-1) micrograms/ml) concentrations of A23187. There was no correlation between the sensitivity of basophils to release in response to anti-IgE and their response to f-met peptide or A23187, in either the MZ or the DZ. We conclude that the ability of basophils to respond to anti-IgE and A23187 is influenced by genetic factors.
Analysis of the fine specificity and cross-reactivity of monoclonal anti-lipid A antibodies.
Authors: Kirkland T N , Colwell D E , Michalek S M , McGhee J R , Ziegler E J 
Published: December 2022

Abstract
We have investigated the fine specificity of anti-lipid A antibodies to identify conserved lipid A antigens. Because lipid A derived from many different Gram-negative bacteria has similar biologic activities, the conserved regions may be of particular importance for the immunostimulatory and toxic properties of lipid A. We found that five of nine antibodies bound to a wide variety of Gram-negative bacteria. All these widely cross-reactive antibodies bound to the same antigenic site within lipid A. Polymyxin B, an inhibitor of lipid A activity, bound to this site as well. The widely cross-reactive antibodies bound to native and base-hydrolyzed lipid A equally well, and also bound to the monosaccharide precursor lipid X. The less cross-reactive antibodies recognized base-hydrolyzed lipid A poorly, and did not recognize lipid X at all. Other investigators have shown that lipid X has some of the activities of lipid A in vitro and can inhibit the lethal toxicity of LPS in vivo. On the basis of this study, we suggest that lipid X contains a conserved lipid A epitope as well.
Natural cellular resistance of beige mice against Cryptococcus neoformans.
Authors: Hidore M R , Murphy J W 
Published: December 2022

Abstract
Previous reports have demonstrated that natural killer (NK) cells are capable of inhibiting the growth of Cryptococcus neoformans in vitro, and recent studies indicate that adoptively transferred NK cell-enriched spleen cell populations enhance clearance of cryptococci from the tissues of cyclophosphamide-pretreated recipients. The primary objective of these studies was to confirm that NK cells participate in early clearance of C. neoformans in vivo. Secondarily, the anti-cryptococcal activities of polymorphonuclear leukocytes and macrophages were examined. Seven-week-old C57BL/6 bg/+ mice, which have normal levels of NK cell activity, were compared with their bg/bg littermates, which have impaired NK cell function. One and 3 days after injecting both groups of mice i.v. with 2 X 10(4) cryptococci, we assessed the NK cell activities in spleens, lungs, and livers and clearance of the organism from corresponding tissues as determined by the mean log10 numbers of cryptococcal colony-forming units (CFU) per organ. Three days postinfection, the mean numbers of cryptococcal CFU in lungs and spleens of bg/+ mice were significantly lower than in the corresponding organs of bg/bg mice. NK cell activities in spleens and lungs of bg/+ mice were significantly higher than were the NK cell activities in similar cell populations from bg/bg mice. In contrast, the mean numbers of cryptococcal CFU in livers of the two groups of animals were nearly equivalent, a situation not unexpected, since liver NK cell activities were extremely low and similar in both groups of animals. Although these data indicated a correlation between early clearance of cryptococci from tissues and levels of NK cell activities in the corresponding tissues, it was also possible that differences in phagocytic cell function between the bg/+ and bg/bg animals could account for the observed differences in clearance of cryptococci from the tissues. Therefore, phagocytic cells from the two groups of animals were compared with respect to their abilities to phagocytize and inhibit the growth of cryptococci and to their abilities to respond to chemotactic stimuli in vivo. Peritoneal PMNL from bg/+ and bg/bg mice were similar in their abilities to phagocytize and inhibit the growth of cryptococci, as well as in their chemotactic responses to viable cryptococci or sodium caseinate. In addition, there were no differences in splenic macrophage functions between the two groups of mice.(ABSTRACT TRUNCATED AT 400 WORDS)
Features of target cell lysis by class I and class II MHC-restricted cytolytic T lymphocytes.
Authors: Maimone M M , Morrison L A , Braciale V L , Braciale T J 
Published: December 2022

Abstract
The lytic activity of influenza virus-specific murine cytolytic T lymphocyte (CTL) clones that are restricted by either H-2K/D (class I) or H-2I (class II) major histocompatibility (MHC) locus products was compared on an influenza virus-infected target cell expressing both K/D and I locus products. With the use of two in vitro measurements of cytotoxicity, conventional 51Cr release, and detergent-releasable radiolabeled DNA (as a measure of nuclear disintegration in the early post-lethal hit period), we found no difference between class I and class II MHC-restricted CTL in the kinetics of target cell destruction. In addition, class II MHC-restricted antiviral CTL failed to show any lysis of radiolabeled bystander cells. Killing of labeled specific targets by these class II MHC-restricted CTL was also efficiently inhibited by unlabeled specific competitor cells in a cold target inhibition assay. In sum, these data suggest that class I and class II MHC-restricted CTL mediate target cell destruction by an essentially similar direct mechanism.
BSF1 induces membrane protein phosphorylation but not phosphoinositide metabolism, Ca2+ mobilization, protein kinase C translocation, or membrane depolarization in resting murine B lymphocytes.
Authors: Justement L , Chen Z , Harris L , Ransom J , Sandoval V , Smith C , Rennick D , Roehm N , Cambier J 
Published: December 2022

Abstract
The findings presented in this study provide evidence that BSF1 receptors and mIg transmit signals via dissimilar transduction mechanisms that result in a common biologic response, hyper-Ia expression. Specifically, BSF1-containing supernatant does not induce PtdInsP2 hydrolysis as determined by measurement of PtdOH and InsP3. Additionally, BSF1 does not stimulate Ca2+ mobilization, PKC translocation from cytosol to membrane, or membrane depolarization. All of these metabolic events appear to play a central role in hyper-Ia expression mediated by mIg and are initiated after treatment of resting B cells with anti-Ig antibodies. In vitro phosphorylation studies with partially purified plasma membranes from resting B cells revealed that BSF1 interaction with membrane receptors stimulates a membrane-associated protein kinase that phosphorylates an endogenous protein of 44 KDa. Anti-Ig does not stimulate phosphorylation of the 44 KDa protein, suggesting that it does not activate the membrane-associated protein kinase. This observation provides the first evidence of a signal transduction mechanism associated with BSF1-receptor ligation. It indicates that although BSF1 does not modulate events associated with PKC activation, it may function via activation of a membrane-associated protein kinase. This provides a focal point for further studies directed at elucidating signal transduction resulting from BSF1-receptor interaction.
Early events in lymphocyte activation as defined by three new monoclonal antibodies.
Authors: Newman W , Fanning V A , Rao P E , Westberg E F , Patten E 
Published: December 2022

Abstract
Three new lymphocyte activation antigens are described whose kinetics of appearance place them very early in the activation pathway. The 78,000 dalton early antigen (Ea) 1 is present at low levels on resting lymphocytes, and its expression is enhanced twofold to threefold within 3 hr of stimulation. Ea2, a nondisulfide-bonded 86,000 and 73,000 dalton heterodimer, is first detectable 3 hr after activation and peaks by 9 hr. Its presence on all but a few cell lines, plus the variable association with a lower m.w. (28,000) structure, suggest that it may serve as a receptor for a growth factor. Neither Ea1 nor Ea2 are restricted to lymphocytes. The 31,000 dalton Ea3 antigen is induced only by PHA but not by other means of activation, and may pre-exist within the cell. The Ea3 antibody blocks PHA-induced but not OKT3-induced mitogenesis, suggesting differences in the pathways of activation by these two stimuli. These reagents, and OKT3, were used to define the cyclosporine A (CSA)-sensitive stage of lymphocyte activation. CSA blocks at a point before the biosynthesis of Ea1 and after that of T3/T cell receptor loss from the cell surface, at a point close to Ea2 biosynthesis.
The role of adherent accessory cells in the generation of effector suppressor T cells.
Authors: Hausman P B , Kawasaki H , O'Hara R M , Minami M , Sherr D H , Dorf M E 
Published: December 2022

Abstract
The role of accessory cell populations in the generation of effector suppressor (Ts3) cells was studied. By using an in vitro culture system, it was previously determined that the induction of NP-specific effector suppressor activity requires T cells, antigen, and an anti-idiotypic B cell population. We now demonstrate that the generation of Ts3 cells in this system also requires accessory cells. The accessory population appears to play a role in the processing and presentation of antigen. These antigen-presenting accessory cells are required early in the induction phase of Ts3 generation. These accessory cells can present NP coupled to immunogenic or non-immunogenic polypeptide carriers, including polymers of L-amino acids. However, NP coupled to polymers of poorly metabolized D-amino acids fail to induce suppressor T cell generation. Furthermore, the data demonstrate that an H-2 homology must exist between the Ts3 precursors and the antigen-presenting cell population if suppressor activity is to be generated. We also characterize the differential genetic restrictions that govern the induction of Ts3 cells that control suppression of either T cell or B cell responses. The data suggest that although I-J region encoded gene products control the induction and effector phases of suppressor cell activity as measured on T cell responses, the suppression of B cell responses appear to be controlled by I-A gene products. Possible cellular mechanisms that might explain these findings are discussed.
Regulation of B cell activation by prostaglandins: cell cycle-specific effects on activation by anti-immunoglobulin and 8-mercaptoguanosine.
Authors: Goodman M G 
Published: December 2022

Abstract
The current studies were undertaken to explore the regulatory effects of macrophages and their soluble products on B cell activation in defined medium by surface membrane-directed mitogens (anti-Ig, LPS) and by intracellular mitogens (8-mercaptoguanosine, [8MGuo]). Supplementation of macrophage-depleted B cell cultures with adherent cells enhanced the response to anti-Ig but depressed the response to 8MGuo. These changes could be eliminated by adding indomethacin to B cell cultures containing supplemental macrophages. Moreover, they could be reproduced by adding exogenous prostaglandins (PGE1, PGE2) but not other macrophage products to cultured B cells. Prostaglandins regulate B cell function (i.e., immunoglobulin secretion) in the same manner as they do mitogenesis. Thus, the polyclonal response to LPS is enhanced, whereas that to 8MGuo is inhibited. We showed previously that anti-Ig acts on a B cell subpopulation distinct from that stimulated by 8MGuo. Moreover, when addition of prostaglandin is delayed for more than 24 hr, the effect on the anti-Ig response changes from enhancement to inhibition and the effect on 8MGuo is lost, suggesting that in the course of activation the cell progresses through a series of cell cycle-specific regulatory states. Additionally, the mitogenic effects of 8MGuo appear to involve larger, cycling cells more than smaller cells. In concert, these data suggest a model for regulation of the B cell cycle in which prostaglandins, whose secretion is elicited by many surface-directed B cell stimuli, enhance the entry of cells into the cell cycle and subsequently regulate their passage through the cycle.
Monoclonal anti-DNA IgM kappa in neuropathy binds to myelin and to a conformational epitope formed by phosphatidic acid and gangliosides.
Authors: Freddo L , Hays A P , Nickerson K G , Spatz L , McGinnis S , Lieberson R , Vedeler C A , Shy M E , Autilio-Gambetti L , Grauss F C 
Published: December 2022

Abstract
Anti-DNA antibodies that cross-react with phosphorylated epitopes of other cellular constituents may be involved in the pathogenesis of autoimmune disease. An IgM monoclonal antibody from a patient with chronic lymphocytic leukemia (CLL) and neuropathy bound to denatured DNA and immunostained myelin in peripheral nerve and spinal cord. The monoclonal IgM bound to ELISA microwells coated with a mixture of phosphatidic acid and gangliosides at serum dilutions of up to 1/100,000, but binding to phosphatidic acid alone was observed at dilutions of less than 1/100 only, and there was no binding to gangliosides alone. Incubation with micelles containing phosphatidic acid and gangliosides selectively absorbed the monoclonal IgM and inhibited its binding to denatured DNA and to myelin. These observations suggest that autoantibodies may bind to conformational epitopes formed by two separate molecules, and that autoantibodies that cross-react with phosphorylated epitopes in DNA and neural tissue could be involved in autoimmune neurologic diseases.
Induction of experimental allergic neuritis in the BN rat: P2 protein-specific T cells overcome resistance to actively induced disease.
Authors: Linington C , Mann A , Izumo S , Uyemura K , Suzuki M , Meyermann R , Wekerle H 
Published: December 2022

Abstract
T lymphocyte lines specific for the peripheral nerve myelin protein P2 were selected from the lymph nodes of Brown Norway (BN) rats immunized with bovine P2 protein in complete Freund's adjuvant. These T cells expressed the W3/25+, OX8-phenotype and responded specifically to bovine P2 protein, but not to PPD or bovine basic protein, in T cell proliferation assays. When injected i.v. into syngeneic recipients, BN P2-specific T cell lines induced both clinical and histologic signs of experimental allergic neuritis (EAN), overcoming the resistance of this rat strain to actively induced EAN. Although the histopathology of the disease was indistinguishable from that seen in T cell-mediated EAN in the Lewis rat, disease onset was considerably later, 7 to 8 days after cell transfer, as opposed to 4 days in Lewis. This lag phase between inoculation and disease onset could not be further reduced even by raising the cell dose to 50 X 10(6) cells/host. The fine specificity of the T cell response to P2 differs between Lewis- and BN-derived T cell lines. At least one neuritogenic epitope for each strain was present in the cyanogen bromide-derived peptide CB2 (residues 21-113), as shown by the ability of CB2-specific T cell lines derived from each strain to transfer EAN to the appropriate host strain. However, neuritogenic BN T lines fail to mount a response to the sequence 53-78 (SP4), which encompasses an epitope that is neuritogenic for Lewis rats. These results demonstrate that the resistance of BN rats to actively induced EAN is not due to the lack of appropriate P2-specific autoreactive T cell clones in the normal T repertoire. Furthermore, the results suggest that two distinct epitopes of P2 are responsible for EAN in Lewis and BN rats.
Transforming growth factor beta is an important immunomodulatory protein for human B lymphocytes.
Authors: Kehrl J H , Roberts A B , Wakefield L M , Jakowlew S , Sporn M B , Fauci A S 
Published: December 2022

Abstract
The growth and differentiation of B cells to immunoglobulin (Ig)-secreting cells is regulated by a variety of soluble factors. This study presents data that support a role for transforming growth factor (TGF)-beta in this regulatory process. B lymphocytes were shown to have high-affinity receptors for TGF-beta that were increased fivefold to sixfold after in vitro activation. The addition of picogram quantities of TGF-beta to B cell cultures suppressed factor-dependent, interleukin 2 (IL 2) B cell proliferation and markedly suppressed factor-dependent (IL 2 or B cell differentiation factor) B cell Ig secretion. In contrast, the constitutive IgG production by an Epstein Barr virus-transformed B cell line was not modified by the presence of TGF-beta in culture. This cell line was found to lack high-affinity TGF-beta receptors. The degree of inhibition of B cell proliferation observed in in vitro cultures was found to be dependent not only on the concentration of TGF-beta added but also on the concentration of the growth stimulatory substance (IL 2) present. By increasing the IL 2 concentrations in culture, the inhibition of proliferation induced by TGF-beta could be partially overcome. In contrast, the inhibition of Ig secretion induced by TGF-beta could not be overcome by a higher concentration of stimulatory factor, demonstrating that the suppression of B cell differentiation by TGF-beta is not due solely to its effects on proliferation. Furthermore, it was demonstrated that B lymphocytes secrete TGF-beta. Unactivated tonsillar B cells had detectable amounts of TGF-beta mRNA on Northern blot analysis, and B cell activation with Staphylococcus aureus Cowan (SAC) resulted in a twofold to threefold increase in TGF-beta mRNA. Supernatants conditioned by unactivated B cells had small amounts of TGF-beta, SAC activation of the B cells resulted in a sixfold to sevenfold increase in the amount of TGF-beta present in the supernatants. Thus, B lymphocytes synthesize and secrete TGF-beta and express receptors for TGF-beta. The addition of exogenous TGF-beta to cultures of stimulated B cells inhibits subsequent proliferation and Ig secretion. TGF-beta may function as an autocrine growth inhibitor that limits B lymphocyte proliferation and ultimate differentiation.