bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of antibody responses by rheumatoid factor. I. Polyclonal activation of human B cells by rheumatoid factor-containing preparations from seropositive plasma.
Authors: Hobbs M V , Morgan E L , Baker N L , Weigle W O 
Published: December 2022

Abstract
Rheumatoid factor (RF)-containing IgM preparations isolated from the plasma of two seropositive patients were able to increase the number of Ig-secreting cells in normal human peripheral blood lymphocyte cultures. This polyclonal B cell activation was optimal in the presence of both T cells and monocytes. A relationship was established between the activator and RF in these preparations based on the ability of both to bind to insolubilized human IgG. The presence of the activator also coincided with the presence of large, RF-containing Ig complexes. These data suggest that RF contributes to the formation of B cell-stimulating immune complexes--a phenomenon with possible negative consequences in disease states characterized by these complexes.
Characterization of in vivo-activated allospecific T lymphocytes propagated from human renal allograft biopsies undergoing rejection.
Authors: Mayer T G , Fuller A A , Fuller T C , Lazarovits A I , Boyle L A , Kurnick J T 
Published: December 2022

Abstract
To evaluate in situ lymphocyte responses in cell-mediated immune tissue injury, we have developed an approach for propagation of human allospecific T lymphocytes directly from tissue biopsies. We have utilized renal allograft tissue obtained from eight patients undergoing cellular rejection. Needle biopsy tissue was cultured in medium containing interleukin 2 (IL 2), including recombinant-DNA-produced IL 2. In each case, lymphoblasts migrated out of the tissue and increased in numbers, especially adjacent to the tissue. In two cases in which there was no cellular infiltrate present in the biopsy, no lymphocytes proliferated in vitro. Instead, fibroblasts eventually filled the wells from these allograft biopsies. The continued presence of the allograft tissue enhanced the viability and growth of the lymphoblasts in cultures from rejecting allografts. The isolated lymphoblasts had surface markers of mature OKT3+ lymphocytes of either OKT4+ or OKT8+ subsets. OKT8+ cells predominated. There was variability (41 to 97%) in the percentage of T lymphoblasts that bore surface HLA-DR antigens. In assays of lymphoblasts obtained from eight separate renal allografts, there was donor-specific cytotoxicity, and in all but two of the cases there was donor-induced proliferation. The specificity of the cytotoxic reaction was tested by using 51Cr-labeled, PHA-stimulated target cells prepared from a panel of HLA-typed donors. Proliferation was tested after 48 hr in the presence of mitomycin C-treated peripheral blood mononuclear cells as stimulator cells by using only 10(4) responder T lymphoblasts. Of particular note was that the cytotoxicity of the isolated lymphoblasts showed specificity against both "private" HLA class I alloantigens (of the allograft donor) as well as "public" cross-reacting epitopes. This method permits the propagation and functional characterization of in vivo-activated T lymphoblasts that are obtained from the actual sites of immune-mediated injury. Preliminary studies of other tissues with diverse inflammatory processes indicate the possible widespread applicability of obtaining in vivo-activated lymphocytes.
Characterization of mononuclear phagocyte subpopulations in the human lung by using monoclonal antibodies: changes in alveolar macrophage phenotype associated with pulmonary sarcoidosis.
Authors: Hance A J , Douches S , Winchester R J , Ferrans V J , Crystal R G 
Published: December 2022

Abstract
Current concepts of pulmonary sarcoidosis suggest that the alveolar macrophage plays a central role in the pathogenesis of the disease. To help define the population of alveolar macrophages in sarcoidosis, we compared the surface phenotype of alveolar macrophages from patients with sarcoidosis and from normal individuals by using monoclonal antibodies (63D3, OKM1, M phi P-9, M phi S-1, 61D3, and M phi S-39) that detect surface antigens on cells of monocyte/macrophage lineage. Although almost all blood monocytes expressed surface antigens detected by each of these antibodies, only a minority of normal alveolar macrophages expressed the same surface antigens (p less than 0.05, each comparison). However, in sarcoidosis, the percentage of alveolar macrophages expressing these surface antigens was increased (p less than 0.05, each comparison with normal alveolar macrophages). Several findings supported the conclusion that the increased expression of these monocyte-lineage surface antigens on sarcoid alveolar macrophages resulted from increased recruitment of monocytes to the lung in sarcoidosis and not from abnormal "activation" of alveolar macrophages. First, alveolar macrophages expressing these antigens had an immature morphology. Second, in vitro cultivation of blood monocytes and alveolar macrophages in the presence of immune and inflammatory mediators, including mediators known to be present in the lung in sarcoidosis, did not prevent the loss of expression of monocyte-lineage surface antigens from monocytes or induce reexpression of monocyte-lineage surface antigens on alveolar macrophages. Third, the expression of monocyte-lineage surface antigens was only increased on sarcoid macrophages from patients whose lower respiratory tract contained an increased number of T lymphocytes, cells known to release monocyte chemotactic factor in sarcoidosis. Consistent with the knowledge that corticosteroids usually suppress the alveolitis of active sarcoidosis, when the expression of alveolar macrophage surface antigens was evaluated before and during therapy, the percentage of alveolar macrophages expressing monocyte-lineage surface antigens returned to normal after 1 to 3 mo of therapy.(ABSTRACT TRUNCATED AT 400 WORDS)
Activation of human thymocytes via the 50KD T11 sheep erythrocyte binding protein induces the expression of interleukin 2 receptors on both T3+ and T3- populations.
Authors: Fox D A , Hussey R E , Fitzgerald K A , Bensussan A , Daley J F , Schlossman S F , Reinherz E L 
Published: December 2022

Abstract
Recent studies have demonstrated that the 50KD T11 molecule is a surface component of a macrophage-independent alternative pathway of human T cell activation that is unrelated to the T3/Ti antigen-MHC receptor complex. Given the expression of T11 on all human thymocytes, it was of interest to determine whether they could be activated via this pathway. The triggering of T11 by monoclonal antibodies anti-T112 and anti-T113, directed at two unique epitopes on the molecule, induced IL 2 receptor expression on both T3+ and T3- thymocytes but did not induce IL 2 production. Consequently, in contrast to peripheral blood T cells, thymocytes did not proliferate in response to anti-T112 and anti-T113 in the absence of exogenous IL 2. These studies suggest that IL 2 receptor gene activation precedes IL 2 gene activation in T cell development. The ability of the alternative pathway of T cell activation to induce IL 2 receptor expression on T3- thymocytes implies that the T11 molecule may have an important role in early thymocyte ontogeny.
Interleukin 1 production by the human monocyte cell line U937 requires a lymphokine induction signal distinct from interleukin 2 or interferons.
Authors: Amento E P , Kurnick J T , Krane S M 
Published: December 2022

Abstract
A soluble product from cloned human T lymphocytes is capable of stimulating U937 cells, a line of human monocytes, to produce interleukin 1 (IL 1). We previously reported that U937 cells exposed to T lymphocyte-conditioned medium secrete mononuclear cell factor (MCF), which increases collagenase and prostaglandin E2 production by adherent rheumatoid synovial cells. Whereas structural and functional homologies between lymphocyte-activating factor (LAF, or IL 1) and MCF were described, previous attempts to measure LAF secretion by lymphokine-stimulated U937 cells were unsuccessful. Although the crude supernatants of cultured U937 cells exposed to medium from lectin-stimulated peripheral blood or cloned T lymphocytes contained MCF activity, no LAF activity was detected. After these crude supernatants were chromatographed on Ultrogel AcA54, however, and the fractions were individually assayed for IL 1, MCF and LAF activities were coeluted with apparent m.w. approximately 14,000 to 23,000. The inability to detect LAF activity in the unfractionated medium was accounted for by an inhibitor of lymphocyte proliferation present in fractions of higher m.w. The T lymphocyte product that stimulated U937 cell maturation and monokine production was secreted in response to lectin-stimulation in a dose-dependent fashion. Although we have previously demonstrated that the hormone 1,25-dihydroxyvitamin D3 caused maturational changes in U937 cells, and other investigators have reported effects of alpha and gamma interferon, these changes are dissociable from IL 1 production. Thus, a distinct lymphocyte-derived signal, necessary for the production of IL 1 by U937 cells, can be identified and dissociated from other biologic products that cause "maturational" changes. The detection of LAF activity in U937 cell supernatants requires the removal of an inhibitor of lymphocyte proliferation.
Purification and physicochemical characterization of murine T cell replacing factor (TRF).
Authors: Takatsu K , Harada N , Hara Y , Takahama Y , Yamada G , Dobashi K , Hamaoka T 
Published: December 2022

Abstract
Murine T cell replacing factor (TRF) was purified from a cellfree supernatant of a T cell hybridoma (B151K12) that constitutively produces TRF. Two assay systems for TRF activity were employed: 1) induction of anti-DNP IgG PFC responses in cultures of splenic B cells from DNP-KLH-primed BALB/c mice, and 2) induction of IgM PFC in chronic B cell leukemic cells (BCL1). The purification scheme consisted of ammonium sulfate precipitation, DEAE-cellulose chromatography, Blue-Sepharose chromatography, hydroxylapatite chromatography, gel permeation with fast protein liquid chromatography (FPLC), and disc polyacrylamide gel electrophoresis. Overall, TRF was purified approximately 34,000-fold with a maximum 3.8% recovery of activity, and the specific activity of the purified TRF was approximately 9.6 X 10(4) U/mg. The TRF that is active in these systems is distinct from the other lymphokines such as IL 1, IL 2, BCGFI (now known as BSFp1), and gamma-interferon. The TRF is extremely hydrophobic, with an apparent m.w. of 50,000 to 60,000 on gel permeation chromatography and 18,000 on SDS-PAGE under reducing conditions. Highly purified B151-TRF abrogated the activity by treatment with trypsin but not with RNase. Moreover, it bound to lima bean agglutinin-Sepharose specific for N-acetylgalactosamine residues, indicating that B151-TRF is a glycosylated glycoprotein containing N-acetylgalactosamine residues. The role of N-acetylgalactosamine residues on TRF activity was additionally substantiated by the fact that the addition of appropriate amounts of N-acetylgalactosamine in the assay systems for TRF preferentially induced a profound suppression for TRF-mediated PFC responses.
Demonstration of structural polymorphism among MB3 light chains by two-dimensional gel electrophoresis.
Authors: Ishikawa N , Kasahara M , Ikeda H , Ogasawara K , Hawkin S , Takenouchi T , Wakisaka A , Kikuchi Y , Aizawa M 
Published: December 2022

Abstract
The heavy and light chain subunits of MB3 molecules were isolated from KT2 (DKT2, DR4, MB3 homozygous), ER (Dw4, DR4, MB3 homozygous), JMe (Dw5, DR5, MB3 homozygous), EBV-Sh (DSh, DRw6.2, MB3 homozygous), and EBV-Ky (DKy, DRw9, MB3 homozygous) cells and were compared with one another by two-dimensional gel electrophoresis. The MB3 light chains from KT2, ER, and EBV-Ky cells were clearly different in terms of their isoelectric points, whereas those from ER, JMe, and EBV-Sh cells were indistinguishable. No differences in charge or m.w. were noted for the MB3 heavy chains from the five cell lines. Thus, three out of the five MB3-positive, D/DR-disparate cell lines were found to express structurally distinct MB3 molecules, demonstrating that MB3 is a public serologic specificity shared by at least three structurally distinct MB (human I-A-like) molecules. Because the DR light chain subunits isolated from EBV-Wa, KT2, ER, JMe, EBV-Sh, and EBV-Ky cells differed from one another in their isoelectric points, the DR light chains were apparently more polymorphic than the MB3 light chains.
Enhanced reactive lysis of paroxysmal nocturnal hemoglobinuria erythrocytes by C5b-9 does not involve increased C7 binding or cell-bound C3b.
Authors: Rosenfeld S I , Jenkins D E , Leddy J P 
Published: December 2022

Abstract
The most complement (C)-sensitive type of erythrocytes (E) occurring in paroxysmal nocturnal hemoglobinuria (type III PNH E) have previously been found to exhibit approximately twofold to fourfold greater lysis than normal human E when exposed to isolated human C5b6, C7, C8, and C9 (reactive lysis), in the absence of a known source of C3- or C5-convertases or fluid-phase C3. In further studies on the mechanism of this phenomenon, we now report that C5b6-dependent binding of 125I-C7 to two samples of PNH E (greater than 95% type III) is equal to that found with normal human E at each of several C5b6 inputs tested. Lysis developed by excess C8 and C9, however, was consistently greater for the PNH E. Thus, the exaggerated sensitivity of type III PNH E to reactive lysis cannot be explained by abnormally high uptake of C5b6 or C7 from the fluid phase. Rather, the data indicate that cell-bound C5b67 sites are converted to effective hemolytic sites with greater efficiency on type III PNH E than on normal human E, assuming that the distribution of cell-bound C7 throughout both cell populations is similar. In related studies we have addressed the proposal by other investigators that C3b putatively bound to PNH E in vivo might account for their increased sensitivity to reactive lysis in vitro, by analogy to prior observations on C3b-potentiated reactive lysis of sheep E. The latter hypothesis was made more appealing by the recent discovery that type III PNH E lack an integral membrane protein, decay-accelerating factor (DAF), which in normal E accelerates the decay of membrane-bound C3 convertases. Against this hypothesis, however, is our present finding that preincubation of PNH E with four different goat or rabbit polyclonal antibodies to human C3 failed to inhibit the subsequent reactive lysis of these cells. Under these same conditions, the C3b-dependent increment in reactive lysis of sheep EAC4b3b was abrogated by pretreatment with similar dilutions of these anti-C3 antibodies, generally in association with agglutination. Furthermore, sheep EAC4b3b displayed increased 125I-C7 binding in proportion to augmented lysis, in contrast to the findings with PNH E. Therefore, deficiency of DAF in type III PNH E does not adequately explain their supranormal sensitivity to reactive lysis unless DAF can modulate the terminal lytic steps by a mechanism distinct from its effect on C3 convertase decay. Alternatively, type III PNH E could have a more general abnormality in which DAF deficiency is one manifestation and increased sensitivity to reactive lysis is another.
Normal function of CR1 on affected erythrocytes of patients with paroxysmal nocturnal hemoglobinuria.
Authors: Roberts W N , Wilson J G , Wong W , Jenkins D E , Fearon D T , Austen K F , Nicholson-Weller A 
Published: December 2022

Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia in which affected erythrocytes (E) are abnormally sensitive to lysis by autologous complement. Affected E from patients with PNH (PNH-E) are deficient in an E membrane regulatory protein of complement, decay-accelerating factor (DAF). Because a functional defect in a second membrane regulatory protein of complement, CR1 (C3b receptor), has also been hypothesized, severely affected PNH-E (type III PNH-E) were tested for abnormalities in CR1 by four methods. E from two patients with 100% type III PNH-E had 3201 and 6783 sites per cell for binding of 125I-labeled rabbit polyclonal F(ab')2 anti-CR1. These values fall within the normal range of CR1 antigenic sites per cell (1267 to 7915, mean = 5,014 +/- 155 SEM) established by assaying the E from 113 healthy donors. The Ka of CR1 on type III PNH-E for 125I-labeled C3b dimer was 2.06 X 10(7) M-1, and the Ka values for the binding of the same ligand to the E from two healthy individuals were 2.45 X 10(7) M-1 and 1.58 X 10(7) M-1. In an assay designed to measure the capacity of human E (Eh) to accelerate the decay of the classical C3 convertase deposited on 1 X 10(7) bystander sheep E (EAC1gp,4bh,2agp), the half-life (t 1/2) of this convertase was diminished from 18.1 min (range 15.2 to 22.9) to 8.1 min (range 7.4 to 8.5) by the addition of 1 X 10(7) normal Eh, to 6.2 min by 100% type III PNH-E, and to 7.5 min by Eh pretreated with an IgG fraction of human antiserum directed against the D antigen of the Rh system. In contrast, Eh (t 1/2 = 7.4) pretreated with a saturating dose of F(ab')2 anti-CR1, and CR1-deficient Eh (less than 10 CR1 molecules/E) from a patient with systemic lupus erythematosus, showed a loss of convertase decay-accelerating capacity to t 1/2 = 11.6 and t 1/2 = 12.4, respectively. Type III PNH-E pretreated with anti-CR1 demonstrated a total loss of their decay-accelerating capacity (t 1/2 = 19.9). In an assay of I cofactor activity, soluble C3b was rapidly converted to iC3b by purified I plus Eh or type III PNH-E, whereas CR1-deficient Eh exhibited less than 5% the I cofactor activity of normal Eh.(ABSTRACT TRUNCATED AT 400 WORDS)
Morphologic and immunologic characterization of human basophils developed in cultures of cord blood mononuclear cells.
Authors: Ishizaka T , Dvorak A M , Conrad D H , Niebyl J R , Marquette J P , Ishizaka K 
Published: December 2022

Abstract
Selective growth of human basophilic granulocytes was obtained in suspension cultures of mononuclear cells from umbilical cord blood. Approximately 50 to 80% of nonadherent cells recovered from 2- to 3-wk-old cultures contained metachromatic granules, and these cells were identified as human basophilic granulocytes by electron microscopy. Histamine content of cultured human basophils was comparable to that in peripheral blood basophils. Cultured basophils bear 2.7 to 3.7 X 10(5) IgE receptors per cell that bind both human IgE and rodent IgE with comparable affinity. Average equilibrium constants of the receptors for human IgE and mouse IgE were 2.56 +/- 0.88 X 10(9) M-1 and 1.85 +/- 0.86 X 10(9) M-1, respectively. The cell-surface component of the IgE receptors on cultured basophils has a m.w. of 64,000. Cultured basophils could be passively sensitized with human IgE and mouse IgE monoclonal antibody, and sensitized basophils released characteristic cytoplasmic granules and both histamine and arachidonate upon challenge with either anti-human IgE or antigen. Incubation of cultured basophils with ionophore A23187 or F-Met-Leu-Phe resulted in histamine release. However, compound 48/80 failed to induce histamine release from the cells.
Complement- and IgE-mediated release of histamine from basophils in vitro. V. Differential effects of drugs modulating arachidonic acid metabolism.
Authors: Farnam J , Grant J A , Lett-Brown M A , Hunt C , Thueson D O , Giclas P C 
Published: December 2022

Abstract
Basophil degranulation probably plays a significant role in the pathogenesis of different hypersensitivity reactions. These cells can be stimulated to secrete lysosomal histamine in vitro in response to various secretagogues. We compared the effects of drugs, modulating arachidonic acid (AA) metabolism, on histamine release (HR) from human basophils stimulated by anti-IgE antibody or C5a anaphylatoxin. Leukocytes from normal donors were preincubated with drug for 15 min at 22 degrees C, followed by the addition of C5a or anti-IgE for 30 min at 37 degrees C. Bromophenacyl bromide, an inhibitor of AA formation by phospholipase, blocked the effects of C5a and anti-IgE (greater than or equal to 3.3 X 10(-6) M, p less than 0.05 and p less than 0.01, respectively). 3-Amino-1-(3-trifluoromethylphenyl)-2-pyrazoline hydrochloride (BW755C, greater than or equal to 3.3 X 10(-5) M) and 5, 8, 11, 14-eicosatetraynoic acid (greater than or equal to 3.3 X 10(-4) M), known inhibitors of both cyclooxygenase (COX) and lipoxygenase (LPX) pathways of AA metabolism, blocked both C5a- and anti-IgE-induced HR (p less than 0.01). Nordihydroguaiaretic acid, an inhibitor of LPX, decreased HR induced by anti-IgE (greater than or equal to 3.3 X 10(-6) M, p less than 0.01) and allergens, but reduced C5a-initiated HR only at a higher concentration (greater than or equal to 7 X 10(-5) M, p less than 0.01). Indomethacin (INDO), an inhibitor of COX, significantly reduced HR caused by C5a (greater than or equal to 3.3 X 10(-8) M, p less than 0.01) and its degradation product C5adesArg, but had no effect or caused slight enhancement of HR initiated by anti-IgE. We confirmed that INDO augments allergen-induced HR. Our findings suggest that there are basic differences in the regulation of C5a- and IgE-mediated basophil degranulation.
Regulation of cell-mediated immunity in cryptococcosis. III. Characterization of second-order T suppressor cells (Ts2).
Authors: Murphy J W , Mosley R L 
Published: December 2022

Abstract
Frequently, patients with systemic cryptococcosis have depressed or absent in vivo or in vitro cell-mediated immune responses to cryptococcal antigen. In addition, these patients have relatively high levels of circulating cryptococcal antigen, which is generally considered indicative of a poor prognosis. Because acquired cell-mediated immunity is an important host defense mechanism in cryptococcosis, we have been studying the effects of cryptococcal antigen on such responses. Using a murine model, we have demonstrated that cryptococcal antigen given i.v. to CBA/J mice, to simulate antigen levels found in patients, can trigger the production of a series of suppressor cells that specifically inhibit anticryptococcal cell-mediated immune responses. Briefly, cryptococcal antigen induces afferent suppressor and/or suppressor inducer (Ts1) cells in the lymph nodes of mice, and the Ts1 cells, or a soluble factor derived therefrom (TsF1), stimulate the production of second-order or efferent suppressor (Ts2) cells. This report provides data that demonstrate that the Ts2 cells were induced in spleens from cyclophosphamide (Cy)-resistant precursors in response to cryptococcal Ts1 cells or TsF1 and that a proliferative process sensitive to Cy was not required for Ts2 induction. The Ts2 cells were detectable 6 days after Ts1 injection, were specific in suppressing the cryptococcal delayed-type hypersensitivity (DTH) response, were T cells with an Lyt-1-,2+,Ia+ (I-J+) phenotype, were effective only on the efferent limb of the cryptococcal DTH response, and mediated their activity via a soluble factor (TsF2). Thus far, the suppressive pathway induced by cryptococcal antigen has characteristics more like those of the suppressor circuits described for the DTH responses to the haptens azobenzenearsonate and 4-hydroxy-3-nitrophenyl acetyl than those of the modulating circuits induced by other antigens. We postulate that a suppressive circuit similar to the one we have defined in the mouse model is operating to suppress the in vivo and in vitro cell-mediated immune responses in cryptococcosis patients who have significant amounts of circulating cryptococcal antigen.