bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lysis of sensitized sheep erythrocytes in human sera deficient in the second component of complement.
Authors: Knutzen Steuer K L , Sloan L B , Oglesby T J , Farries T C , Nickells M W , Densen P , Harley J B , Atkinson J P 
Published: December 2022

Abstract
Analysis of C-dependent lysis of sensitized SRBC by C2-deficient sera (C2D) led to the characterization of a C2 bypass pathway. Lysis in the total hemolytic C assay by C2D sera was Ca2+-dependent and required a high concentration of hemolysin to sensitize E. Selective component depletion indicated a requirement for C1 and C4 of the classical pathway (CP) and proteins B, P, and probably D of the alternative pathway (AP). Total hemolytic C could be restored to normal in these C2D sera by utilizing heavily sensitized E or by the addition of a supranormal concentration of B. This system most closely resembles a pathway described by J. E. May and M. M. Frank which requires antibody, C1, and the AP but not C4 or C2. It differs in its requirement for C4. We hypothesize that this pathway represents vestiges of a more primitive C pathway. It becomes evident and possibly clinically important in the setting of C2 deficiency, by allowing C activation, other than the AP, and perhaps in normal individuals, by damaging microorganisms that have evolved means to inhibit early components of the CP.
The effect of IFN-gamma and colony-stimulating factors on the expression of neutrophil cell membrane receptors.
Authors: Buckle A M , Hogg N 
Published: December 2022

Abstract
The recombinant cytokines IFN-gamma, granulocyte-macrophage (GM)-CSF, and granulocyte (G)-CSF are all known to affect the function of neutrophils. We have investigated their ability to alter the surface expression of neutrophil Fc gamma R and CR. FcRI, formerly considered to be mononuclear phagocyte specific, was found on a variable percentage of neutrophils after 12 h of tissue culture. These levels could be readily enhanced by IFN-gamma at 0.5 U/ml suggesting that neutrophil FcRI is extremely sensitive IFN-gamma. In addition, membrane expression of FcRIII, the most abundant receptor of neutrophils, could also be increased by IFN-gamma and by GM-CSF and G-CSF. However, the opposite effect was observed in samples in which the initial levels of FcRIII were high. In these situations IFN-gamma and GM-CSF caused a decrease in receptor expression. No consistent alterations were found in the levels of FcRII. Cytokine-induced increases in both FcRI and FcRIII were not evident within the first hour of treatment suggesting that these molecules are not available in an intracellular compartment but must be newly synthesized. In contrast, the CR, CR1 and CR3, could be rapidly induced by GM-CSF indicating that this cytokine causes the mobilization of preformed molecules to the membrane. G-CSF and IFN-gamma did not alter the expression of CR1 and CR3. Thus, the very different effects of IFN-gamma, GM-CSF, and G-CSF suggest that the neutrophil functional profile will be distinctively affected by exposure to each of these cytokines.
Secretion of colony-stimulating factors by T cell clones. Role in adoptive protection against Listeria monocytogenes.
Authors: Magee D M , Wing E J 
Published: December 2022

Abstract
CSF have been postulated to be important mediators of host defenses. The current studies were undertaken to investigate the production of CSF by Listeria-specific, T cell clones and to assess the participation of CSF in anti-listerial host resistance. Listeria-specific L3T4+, Lyt-2- T cell clones were isolated and expanded by standard techniques. The clones themselves protected mice from listerial challenge when injected intravenously, and supernatants generated from Ag-stimulated clones were protective. In order to define factors important in the protection, supernatants from the clones were assayed for CSF by several in vitro assays. Total colony-stimulating activity was measured with a bone marrow colony-forming assay. T cell clones secreted 1000 to 2000 U/ml of colony-stimulating activity after 48 hours of stimulation with specific antigen. The relative amounts of the various CSF were determined by the capacity of supernatants to support proliferation of the factor-dependent cell lines FDCP-1 and 32D cl 3 in the presence and absence of specific anti-CSF antibodies. Results showed that most of the CSF activity was due to granulocyte-macrophage (GM)-CSF and IL-3. The role of GM-CSF in anti-listerial host resistance was assessed in two types of experiments. In one set of experiments GM-CSF activity was neutralized in the supernatants by addition of specific rabbit anti-GM-CSF antibodies. Treated and untreated supernatants were then tested for their capacity to protect nonimmune mice against listerial challenge. Neutralization of GM-CSF in the supernatants decreased the protective capacity of the supernatants by approximately 23%. In a second set of studies, the administration of recombinant murine GM-CSF was shown to protect mice from challenges of L. monocytogenes. Taken together, these experiments provide evidence that CSF are important mediators of immune T cell mediated host defenses.
MHC restriction of the antibody repertoire to secretory antigens, and a major allergen, of the nematode parasite Ascaris.
Authors: Tomlinson L A , Christie J F , Fraser E M , McLaughlin D , McIntosh A E , Kennedy M W 
Published: December 2022

Abstract
Humans vary considerably in the antigen specificity of their immune responses to parasitic nematodes, and in the infection loads of individuals living in the same environment. The possibility that the former has a genetic basis operating through repertoire control of the immune system was investigated using infection of mice with the nematode Ascaris. The specificity of the antibody response was examined using excretory/secretory (ES) materials of the parasite as target Ag. No strain of mouse was found to recognize all of the potentially antigenic components of ES, and the Ag recognition patterns varied considerably from strain to strain. Using H-2 congenic mice on both the BALB and B10 backgrounds, it was established that the antigen recognition patterns were MHC-determined. Focusing on one particular component of ES, of Mr 14,000, only H-2s strains responded in IgG. This MHC restriction of the repertoire was confined to infection, and broke down under adjuvant-assisted immunization with the purified protein. The Mr 14,000 molecule was also found to be a potent allergen in a passive cutaneous anaphylaxis assay, and the IgE response to it was also restricted to H-2s. This haplotype was, however, a low IgE responder on the SJL background. There is, therefore, MHC control of the specificity of the immune response to this molecule, but non-MHC control of the amplitude of the IgE antibody response to it. Hybrids between responder and nonresponder strains (BALB/c x SJL)F1, responded to the Mr 14,000, but their responses to other ES components could not be predicted from the response patterns of parental strains. For example, the BALB/c parent responded to a 118-kDa component, but the SJL parent and the F1 progeny did not. Moreover, the response to a 41-kDa Ag was substantially down-regulated in the F1, whereas both parental strains responded vigorously. This new model system, therefore, has implications for MHC control of responses to the allergens of pathogens, and for the complex immunoregulation in heterozygotes in the context of infection.
Induction of activation antigens on human natural killer cells mediated through the Fc-gamma receptor.
Authors: Harris D T , Travis W W , Koren H S 
Published: December 2022

Abstract
NK cells, defined here as lymphocytes bearing the CD16 Ag found on the NK cell Fc-gamma receptor (FcR), are known to enter a proliferative and activated state in response to stimulation with IL-2 as assessed by clonal expansion, short-term DNA synthesis, and de novo expression of lymphocyte-associated activation Ag. We have found that the FcR of NK cells acts as a signaling pathway through which IL-2-dependent activation may be greatly enhanced, allowing for more rapid induction of activation Ag and recruitment of an increased percentage of cells expressing surface markers of cellular activation. FcR-interactive agents, such as solid phase immobilized immune complexes or cross-linked CD16-specific mAb, work synergistically with rIL-2 to elicit a rapid expression of IL2R and transferrin receptors on greater than 50% of purified NK cells as early as day 3 of culture. IL-2 or FcR-interactive stimuli alone were weak or ineffective stimulators by comparison. In contrast to the induction of de novo activation Ag, DNA synthesis was elicited by IL-2 alone, but was not substantially or consistently enhanced by the subsequent addition of FcR-interactive stimuli.
Anti-T12, an anti-CD6 monoclonal antibody, can activate human T lymphocytes.
Authors: Gangemi R M , Swack J A , Gaviria D M , Romain P L 
Published: December 2022

Abstract
Anti-T12 is a murine IgM mAb that recognizes the 130-kDa CD6 glycoprotein on mature human T lymphocytes. Examination of the in vitro effects of this mAb on freshly isolated T cells demonstrates that anti-T12 can induce T cell activation. Such activation is macrophage-dependent, and optimal stimulation occurs with 0.2 to 5 micrograms/ml of purified mAb. This response to soluble mAb is detectable at day 4 to 5 of culture, and peak [3H]TdR uptake is observed at day 7. In a highly similar fashion, the mAb causes a marked augmentation of the autologous mixed lymphocyte reaction, without altering the kinetics of that response. Although optimal anti-CD3 mAb induced mitogenesis is unaffected by anti-T12, suboptimal stimulation of macrophage-depleted T cells by small amounts of immobilized anti-CD3 can be dramatically enhanced when anti-CD3 and anti-T12 are cross-linked together. A soluble nonmitogenic anti-CD3 mAb completely inhibits anti-T12-mediated T cell activation. IL-2R expression is induced by anti-T12 stimulation in 10 to 30% of T cells, and T cell proliferation is substantially inhibited by anti-IL-2R mAb, indicating that anti-T12 induced T cell activation and proliferation utilizes an IL-2-dependent pathway. Isolated CD4+ but not CD8+ cells are stimulated to proliferate, but the CD8+ cells in unseparated T cell preparations activated by anti-T12 do proliferate comparably to the CD4+ cells in such cultures. These data indicate that relatively weak activation of T cells via the TCR/CD3 complex may be augmented significantly by CD6-mediated signals induced by the anti-T12 mAb. The findings suggest that the CD6 T cell membrane protein may have the capacity to function as a physiologically important structure involved in the regulation of T cell activation.
Dual role of the CD44 molecule in T cell adhesion and activation.
Authors: Shimizu Y , Van Seventer G A , Siraganian R , Wahl L , Shaw S 
Published: December 2022

Abstract
Studies of T cell adhesion and activation reveal two new functions of the CD44 molecule, a molecule now recognized to be identical to three molecules of functional interest: Pgp-1, Hermes, and extracellular matrix receptor type III (ECMRIII). By screening for mAb which inhibit T cell adhesion to E, we have identified a functionally unique CD44-specific mAb, NIH44-1, which partially inhibits T cell rosetting by binding to CD44 on the E. NIH44-1, which immunoprecipitates a protein of 85 to 110 kDa with broad tissue distribution, was determined to be specific for CD44 based on comparison of its tissue distribution with multiple CD44-specific reference mAb and sequential immunoprecipitation with such mAb. Anticipating a role for many adhesion molecules in signal transduction, we studied the effect of CD44 mAb on T cell activation and observed that CD44 mAb dramatically augments T cell proliferation induced by CD3- and CD2-receptor-mediated activation. The augmentation of the response to immobilized CD3 mAb by exhaustively monocyte-depleted T cells indicates that augmentation can be mediated by binding to the T cell. Thus, our studies demonstrate specific new roles for CD44 in T cell adhesion and activation. Furthermore, we suggest that: 1) CD44 has a role in adhesion of cells of multiple lineages; and 2) CD44 may participate in adhesion not (only) by functioning as an adhesion receptor but rather by serving as an anchorage site for other adhesion molecules.
DBA/2J and DBA/2Ha lymphocytes differ in their ability to induce graft-vs-host disease.
Authors: Fast L D 
Published: December 2022

Abstract
Graft-vs-host disease (GVHD) is a common occurrence after bone marrow transplantation despite the use of MHC-matched donors and recipients. This indicates that non-MHC loci play an important role in the regulation and development of GVHD. Non-MHC loci have been shown to regulate GVHD in a murine model where acute GVHD results from i.v. injection of C57BL/6J spleen cells into B6D2F1/J [C57BL/6J X DBA/2J)F1) recipients while chronic GVHD results from injection of DBA/2J spleen cells. In contrast to the hyperproduction of Ig and auto-antibodies that is characteristic of the chronic GVHD that occurs after injection of DBA/2J cells, injection of DBA/2Ha cells was found to induce CTL and suppressor cells characteristic of the acute GVHD that results from injection of C57BL/6 cells into B6D2F1/J recipients. Genetic analysis indicated that one autosomal locus is responsible for the different GVHD responses of DBA/2J and DBA/2Ha cells and that the DBA/2Ha allele is dominant. Further studies indicate that the different responses by DBA/2J and DBA/2Ha cells is not due to functional differences between the two sets of cells but by a radiosensitive B6D2F1 recipient immune response which discriminates between the DBA/2J and DBA/2Ha spleen cells.
Low molecular weight B cell growth factor-responsive cloned human B cell lines. I. Phenotypic differences and lack of requirement for CD23 (Fc epsilon RII).
Authors: Warrington R J , Rutherford W J , Wong S K , Cook J M , Rector E S 
Published: December 2022

Abstract
The EBV-transformed B cell line JR-2 proliferates in response to partially purified preparations of low m.w. B cell growth factor (LMW-BCGF). Two clones of JR-2 were generated that retained this LMW-BCGF responsiveness, exhibiting similar dose/response characteristics but differing phenotypically. The B10 clone grows as single, discrete, small round cells, whereas D3 grows in aggregates. The clones also differ in the expression of cell surface Ag, D3 being weakly DR+ and strongly CD23+, whereas B10 lacks these Ag. The CD23 on D3 cells binds IgE. Both clones are T9+, 4F2+, B1-, B2- and CALLA-. D3 expresses surface IgG and differentiates in the presence of LMW-BCGF, to secrete IgG. B10 lacks surface and cytoplasmic Ig and fails to differentiate in response to LMW-BCGF. CD23 cannot be induced on B10 by incubation with either LMW-BCGF or IL-4. B10 does not shed CD23 and shed CD23 is not a growth factor for either cloned line. Expression of CD23 on D3 cells is not affected by preincubation with LMW-BCGF. Neither B10 or D3 cells respond to rIL-1, rIL-2, rIL-4, rIL-6, rTNF-alpha/beta, rIFN-gamma, or to high m.w. BCGF (Namalwa), alone or in combination. Both clones absorb BCGF activity and crossover absorptions indicate that the clones remove growth factors required by each other. D3 and B10 both appear therefore to respond selectively to LMW-BCGF. These data suggest that the loss of CD23 from a cloned derivative of the cell line JR-2, although accompanied by considerable phenotypic change, is not associated with the disappearance of LMW-BCGF responsiveness, indicating that CD23 is not the essential receptor for LMW-BCGF.
C-reactive protein reacts with the U1 small nuclear ribonucleoprotein.
Authors: Du Clos T W 
Published: December 2022

Abstract
C-reactive protein (CRP) was found to produce a small, discrete, speckled fluorescence pattern in the nucleus of HEp-2 cells. Double staining with anti-RNP serum and CRP produced very similar staining patterns. By counterimmunoelectrophoresis CRP was bound to extractable nuclear antigens found in rabbit thymus extract. The reactive components of the extract were only partially sensitive to treatment with RNase. CRP immunoprecipitated the U1 RNA species from [32P]labeled HeLa cells and the protein bands of the Sm/RNP complex from [35S]-methionine-labeled HeLa cells. By blotting, CRP bound to several discrete bands in a calcium-dependent, PC-inhibitable manner. Two of the bands comigrated with the 70K protein band associated with the U1 snRNP, and its major breakdown product. Binding to these bands was inhibited by both EDTA and PC indicating that CRP binds these proteins through the PC-binding site. Binding to the 70K protein of the U1 snRNP was confirmed by reactivity with the recombinant 70K protein in a dot blot. These findings indicate the CRP binds to the U1-RNP snRNP particle. Considering the ability of CRP to inhibit antibody responses to its ligands and its ability to activate C and promote phagocytosis it is suggested that CRP may play a role in the regulation of autoantibody responses to nuclear Ag.
Bactericidal defect of neutrophils in a guinea pig model of thermal injury is related to elevation of intracellular cyclic-3',5'-adenosine monophosphate.
Authors: Bjornson A B , Knippenberg R W , Bjornson H S 
Published: December 2022

Abstract
PG of the E series inhibit major effector functions of polymorphonuclear leukocytes (PMN) by elevating intracellular cAMP. The present study investigated the involvement of this mechanism in the bactericidal defect of PMN induced by thermal injury in a guinea pig model. Peripheral and peritoneal exudate PMN harvested from thermally injured guinea pigs at 1 or 2 days postburn had decreased bactericidal activity against Pseudomonas aeruginosa and a marked increase in cAMP content. Production of PGE1 by these cells in the absence of exogenous PMN activators was also increased. Treatment of PMN in vitro or in vivo with nonsteroidal anti-inflammatory drugs (indomethacin, ibuprofen, and piroxicam) restored bactericidal activity to normal and concomitantly reduced cAMP content and PGE1 production. A concomitant reduction in cAMP content and PGE1 production was also observed as bactericidal activity of PMN returned to normal under natural conditions during 4 to 7 days postburn. The enhancement of PMN bactericidal activity mediated by NSAID was fully counteracted by purified PGE1, theophylline, and by cAMP itself. These results suggest that the bactericidal defect of PMN induced by thermal injury is related to elevation of cAMP and that PGE1 plays a significant role in this phenomenon.
The rise in concentration of free Ca2+ and of pH provides sequential, synergistic signals for secretion in antigen-stimulated rat basophilic leukemia (RBL-2H3) cells.
Authors: Ali H , Collado-Escobar D M , Beaven M A 
Published: December 2022

Abstract
Ag stimulation of rat basophilic leukemia (RBL-2H3) cells results in hydrolysis of inositol phospholipids, a transient increase in concentration of cytosol Ca2+ [( Ca2+]i), a gradual increase in cytosolic pH (pHi) and the activation of protein kinase C. To determine whether all these changes serve as signals for secretion, studies were conducted with cells permeabilized with streptolysin O in which pHi and [Ca2+]i could be varied independently of each other and enzyme activities could be manipulated. At resting pHi (approximately 7.0) and [Ca2+]i (0.1 microM), the permeabilized cells showed little secretory response to Ag. At resting pHi, elevated levels of Ca2+ (0.33 microM) were required for maximal secretory response to Ag. At a pHi of 7.4, however, 0.1 microM [Ca2+]i was sufficient to sustain near maximal responses to Ag. Therefore, a small increase of [Ca2+]i to 0.33 microM was required to initiate secretion, but once the pHi was elevated secretion could be sustained at near basal levels of [Ca2+]i. Since elevating the [Ca2+]i and pHi, by themselves promoted little secretion, another potentiating signal must have been generated by antigen stimulation. This signal was possibly transduced via hydrolysis of inositol phospholipids and protein kinase C. Even with an elevated [Ca2+]i (0.33 microM) the hydrolysis of the phospholipids and secretion stimulated by Ag were inhibited by guanosine 5'(2-O-thio)diphosphate and neomycin. Furthermore, both protein-kinase C and the secretory response to Ag were lost after permeabilized cells were washed but both were retained if cells were exposed to PMA before permeabilization.
Characterization of T cell antigens associated with the cell wall protein-peptidoglycan complex of Mycobacterium tuberculosis.
Authors: Barnes P F , Mehra V , Hirschfield G R , Fong S J , Abou-Zeid C , Rook G A , Hunter S W , Brennan P J , Modlin R L 
Published: December 2022

Abstract
Mycobacterium tuberculosis cell walls are likely to contain critical T cell Ag capable of inducing protective immunity against the development of tuberculosis in animal models. Therefore, we characterized cell wall-associated Ag that stimulate T lymphocytes in tuberculosis patients and clinically well tuberculin-positive individuals. A protein-peptidoglycan complex isolated from the M. tuberculosis cell wall had potent immunologic activity, evoking PBMC proliferative responses similar to those induced by sonicated whole M. tuberculosis. In order to characterize the immunoreactive protein determinants associated with the protein-peptidoglycan complex, T cell lines were established to cell wall Ag and used to probe M. tuberculosis proteins separated by SDS-PAGE. These T cell lines proliferated primarily to protein Ag of 10, 19, 23, 28, 30, 40 to 50, and 65 kDa. Cell wall-reactive T cell clones that recognized the 10-, 23-, 28-, and 30-kDa proteins as single bands on SDS-PAGE did so under reducing and nonreducing conditions, suggesting that these are not proteolytic fragments or subunits of larger protein aggregates. We propose that these protein monomers, when post-translationally complexed with peptidoglycan, are the key ingredients of the immunogenic protein-peptidoglycan complex. In order to assess the relationship of the cell wall-associated Ag to those secreted proteins from "early culture filtrates" of actively growing M. tuberculosis recently implicated in eliciting protective immunity, cell wall-reactive T cell clones were tested for their ability to recognize early culture filtrates. Results revealed that at least three proteins shared with the cell wall complex are contained within early culture filtrates. Our data indicate that antigenic determinants associated with the protein-peptidoglycan complex of the M. tuberculosis cell wall may be involved in protective immunity and hence are potential candidates for inclusion in an effective antituberculosis vaccine.