bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of lymphocyte homing. I. Alterations in homing receptor expression and organ-specific high endothelial venule binding of lymphocytes upon activation.
Authors: Hamann A , Jablonski-Westrich D , Scholz K U , Duijvestijn A , Butcher E C , Thiele H G 
Published: December 2022

Abstract
Upon activation, lymphocytes display profound alterations in their in vivo migration behavior. In an attempt to understand some of the cellular mechanisms responsible for this altered behavior, in vitro stimulated lymphocytes have been analyzed for their expression of a putative homing receptor (HOR) (defined by mAb MEL-14) and for their ability to bind to specialized lymphoid organ high endothelial venules (HEV) in vitro. The results indicate that signals related to lymphocyte activation induce complex alterations in HOR expression and organ-specificity of HEV-binding: 1) submitogenic stimuli induce an increase in MEL-14 antigen expression. This applies to almost all lymphocytes in autologous cultures, for the fraction of cells in periodate, LPS- or Con A-treated cultures not fully activated and for cultures stimulated with suboptimal doses of Con A. 2) Full blast transformation is associated with a decrease or complete loss of MEL-14 antigen expression on the majority of blasts in all activating systems used, but a subset of up to 30 to 40% of fully activated cells may nonetheless express very high levels of the MEL-14 antigen. 3) Functional assays reveal that Con A and periodate stimulation lead to a selective, nearly complete suppression of the lymphocytes binding to HEV of Peyer's patches, even under conditions where overall binding to peripheral node HEV is increased. This indicates a differential regulation of the two respective receptors, with the mucosa system-specific HOR being more prone to down-regulation during in vitro activation by these mitogens.
Autoreactive T cells in mercury-induced autoimmunity. Ability to induce the autoimmune disease.
Authors: Pelletier L , Pasquier R , Rossert J , Vial M C , Mandet C , Druet P 
Published: December 2022

Abstract
It has been previously shown that autoreactive T cells appear during mercury-induced autoimmunity in Brown-Norway (BN) rats. In the present work, it is shown that: 1) T cells and T helper cells from HgCl2-injected BN rats are able to actively transfer autoimmunity in normal BN rats; the disease transferred is exacerbated when recipients are treated with the antisuppressor/cytotoxic T cell monoclonal antibody (OX8); 2) normal T cells preincubated with HgCl2 are also able to transfer the disease in OX8-treated but not in T cell-depleted rats; and 3) T cells from HgCl2-injected BN rats also transferred the disease in both normal and T cell depleted rats. It is concluded that: 1) autoreactive T cells, and presumably anti-Ia T cells are involved in the pathogenesis of mercury-induced autoimmunity; 2) these autoreactive T cells induce suppressor/cytotoxic T cells to proliferate in normal syngeneic recipients; the fact that this T cell subset did not proliferate in HgCl2-injected BN rats suggests that HgCl2 also affects T suppressor cells; and 3) mercury-induced autoimmunity could result from the additive effect of the emergence of autoreactive T cells and of a defect at the T suppressor level.
Effects of human recombinant tumor necrosis factor-alpha and interleukin 1 on the synthesis of glycosaminoglycan and DNA in cultured rat costal chondrocytes.
Authors: Ikebe T , Hirata M , Koga T 
Published: December 2022

Abstract
We examined effects of human rTNF alpha on the synthesis of glycosaminoglycan and DNA in cultured rat costal chondrocytes. The effects of human recombinant IL-1 alpha and IL-1 beta were also given attention. rTNF alpha, as well as rIL-1 alpha and rIL-1 beta, decreased the incorporation of [35S]sulfate into glycosaminoglycan to about 10% of the levels in the control. The half-maximal doses of rTNF alpha, rIL-1 alpha or rIL-1 beta required for the suppression of glycosaminoglycan synthesis (by rTNF alpha, rIL-1 alpha, and rIL-1 beta) were 2 ng/ml, 30 ng/ml, or 5 ng/ml, respectively. rTNF alpha stimulated incorporation of [3H]thymidine in the chondrocytes in a dose- and time-dependent manner. DNA synthesis was increased to about threefold over the control cultures in the presence of 1 microgram/ml rTNF alpha for 72 hr. The stimulatory effect of rTNF alpha on DNA synthesis was observed in both subconfluent and confluent cultures, whereas rIL-1 alpha and rIL-1 beta had no stimulatory activity on DNA synthesis. The addition of rTNF alpha to the cultures of chondrocytes stimulated DNA synthesis, even in medium containing no fetal calf serum. The fetal calf serum acted synergistically with rTNF alpha in increasing DNA synthesis. We propose that both TNF and IL-1 may be involved in inflammatory diseases of cartilage, and that TNF alpha, but not IL-1, may have some physiologic growth factor function for chondrocytes.
Novel receptor-mediated internalization of interleukin 2 in B cells.
Authors: Tanaka T , Saiki O , Doi S , Fuji M , Sugamura K , Hara H , Negoro S , Kishimoto S 
Published: December 2022

Abstract
Novel IL-2-binding molecules (p70 and p75) mediating internalization and degradation of IL-2 were examined by employing a human B lymphoblastoid line, SKW6-4 cells. High concentrations of IL-2 induced IgM secretion in these cells through a receptor distinct from Tac antigen. The acid-wash technique revealed that more than 60% of 125I-labeled IL-2 bound to the cells became acid-unremovable in the first 30 min of incubation at 37 degrees C and degradation products of 125I-IL-2 increased after 30 min of incubation. Treatment of the cells with NaN3 buffer inhibited the appearance of acid-unremovable 125I-IL-2, suggesting that acid-unremovable 125I-IL-2 was not due to fluid-phase pinocytosis but due to internalization. Loss of labeled bands by incubation of cells with 125I-IL-2 at 37 degrees C before affinity cross-linking demonstrated that 125I-IL-2 was internalized via novel IL-2-binding molecules. These results suggest that novel IL-2-binding molecules are responsible for internalization and may mediate signal transduction in B cells in the absence of Tac antigen.
Mapping of HLA epitopes recognized by H-2-restricted cytotoxic T lymphocytes specific for HLA using recombinant genes and synthetic peptides.
Authors: Pala P , Corradin G , Strachan T , Sodoyer R , Jordan B R , Cerottini J C , Maryanski J L 
Published: December 2022

Abstract
Immunization of DBA/2 (H-2d) mice with syngeneic P815 tumor cell transfectants that express HLA class I genes elicits CTL that recognize HLA in the context of H-2Kd molecules. Anti-HLA-CW3 CTL cross-react to a variable extent on the related alleles A3 and A24. Using a panel of target cells expressing native or recombinant HLA genes, we could map the epitope recognized by a CTL clone specific for CW3 to the second external (alpha 2) domain of CW3. Moreover, the epitope recognized by this clone could be mimicked by incubating P815 (HLA negative) target cells with a synthetic peptide corresponding to the C-terminal 12 amino acids of the CW3 alpha 2 domain (residues 171 to 182). Other independent anti-CW3 CTL clones with different fine specificities recognized the same CW3 peptide. In contrast, CTL clones specific for HLA-A24 or HLA-A3 that did not lyse P815-CW3 transfectants did not recognize this peptide. The CW3 peptide could be recognized on other tumor cell targets that were also of H-2d origin, but not on those of H-2b or H-2k origin. The requirement for the expression of H-2Kd by the target cells was directly demonstrated using L cell Kd transfectants. Our results suggest that the CTL response of DBA/2 mice immunized with P815-CW3 transfectants is predominantly Kd restricted and focused on epitopes contained within the 12 C-terminal amino acids of the alpha 2 domain.
The B cell-associated CD37 antigen (gp40-52). Structure and subcellular expression of an extensively glycosylated glycoprotein.
Authors: Schwartz-Albiez R , Dörken B , Hofmann W , Moldenhauer G 
Published: December 2022

Abstract
The human B lymphocyte-associated CD37 antigen (gp40-52) has been characterized by the monoclonal antibody HD28. The CD37 antigen is strongly expressed on surface immunoglobulin positive B lymphocytes and weakly on a subpopulation of T lymphocytes and myeloid cells. The total molecular mass of the antigen ranges from approximately 40 to 52 kDa in B cell-derived leukemias and malignant lymphomas as well as in normal and anti-mu/B cell growth factor-activated tonsillar B cells. The polydisperse nature of the electrophoretic pattern of the CD37 antigen was found to be due to a microheterogeneity in its carbohydrate moiety. Biochemical analysis showed that the CD37 antigen derived from B cell-lines BJAB and LICR-LON-HMy2 consists of a single chain protein core of approximately 25 kDa to which two N-linked, complex carbohydrate antennae of various length are bound. The glycosylation of the molecule comprises about 50% of the total molecular mass. The molecule does not contain O-linked carbohydrate chains. In contrast, the non-Hodgkin's lymphoma cell line, OCI.LY1, which is growth-dependent on human serum, carries a CD37 antigen with an additional carbohydrate chain resulting in a total molecular mass of approximately 40 to 64 kDa. At the electron microscopy level, this cell surface-expressed antigen was found to be associated with intracellular vesicles. The subcellular distribution of the CD37 antigen may reflect a function of this antigen both at the cell surface and in the cytoplasm. We found that, both due to its peculiar biochemical structure and its ultrastructural distribution, the CD37 antigen closely resembles the 46-kDa species of the mannose 6-phosphate receptor. The implications of this possible congruence for the function of the CD37 antigen are discussed.
Proliferation and production of IL-2 and B cell stimulatory factor 1/IL-4 in early fetal thymocytes by activation through Thy-1 and CD3.
Authors: Tentori L , Pardoll D M , Zuñiga J C , Hu-Li J , Paul W E , Bluestone J A , Kruisbeek A M 
Published: December 2022

Abstract
To examine which cell surface molecules can operate as transducers of activation signals to early fetal thymocytes, we analyzed the ability of mAb to CD3 and Thy-1 to induce fetal thymocyte activation. Both proliferation and lymphokine secretion were used as measures of activation. We show that anti-CD3 antibodies induce activation of fetal thymocytes as early as day 13 of fetal thymus development, 2 days before CD3 can be detected by flow cytometry. In addition, an alternative activation signal can be delivered to fetal thymocytes through the Thy-1 molecule as early as it is expressed, i.e., day 13. Both CD3- and Thy-1-mediated activation of day 15 fetal thymocytes results in expansion of cells expressing a CD3-gamma delta receptor complex; no CD3-alpha beta receptor complex could be detected. IL-2 production induced by CD3- and Thy-1-induced activation of fetal thymocytes is evident at the 13th day of gestation. Finally, an additional lymphokine B cell stimulatory factor-1 (BSF-1)/IL-4 (so far known only to be produced by mature CD3- cells), is also produced by fetal thymocytes. The results demonstrate that at least two cell surface molecules, Thy-1 and CD3, can function as pathways of activation in fetal thymocytes, and that at least two lymphokines, IL-2 and BSF-1/IL-4, are produced upon activation. These findings may well reflect a role for the early appearance of CD3- cells in thymus ontogeny.
Antigen-specific inhibition of immune interferon production by suppressor cells of autoimmune encephalomyelitis.
Authors: McDonald A H , Swanborg R H 
Published: December 2022

Abstract
Previous work from this laboratory has revealed that spleen and/or lymph node cells from Lewis rats, that have recovered from an acute episode of experimental autoimmune encephalomyelitis (EAE), suppress the development of EAE when injected into syngeneic recipients subsequently challenged with myelin basic protein (MBP) in CFA. In an effort to understand the mechanism of this suppression, we measured the production of immune IFN-gamma, which may be required for the induction of an immune response, by EAE effector T cells (which transfer disease) and EAE suppressor cells when cultured in vitro with MBP. We now report that EAE effector T cells produce IFN-gamma when cultured in vitro with MBP. In contrast, spleen cells from recovered rats (which manifest suppressor activity in vivo) do not produce IFN-gamma. Moreover, in cell mixing experiments, these suppressor spleen cells inhibited the production of IFN-gamma by EAE effector cells. This inhibition was not eliminated by the removal of macrophages nor by the inhibition of PG synthesis by indomethacin. Furthermore, the inhibition was shown to be Ag-specific and mediated by nylon-adherent, radiation-sensitive splenic T cells. The findings suggest that suppressor cells regulate EAE by inhibiting IFN-gamma production by effector cells. This inhibition may result in the down-regulation of IFN-gamma-induced expression of class II major histocompatibility Ag on cells of the central nervous system, thus reducing the presentation of tissue-specific Ag (i.e., MBP) to autoreactive lymphocytes.
Lack of an obligate role for IFN-gamma in the primary in vitro mixed lymphocyte response.
Authors: Bucy R P , Hanto D W , Berens E , Schreiber R D 
Published: December 2022

Abstract
We have investigated the relative importance of two lymphokines, IL-2 and IFN-gamma, in the primary murine MLR. Three separate lines of evidence indicate that IL-2 and not IFN-gamma is the relevant lymphokine for both proliferation and activation of CTL in these cultures. No obligate role for IFN-gamma was found. First, CTL activation in the presence of high dose cyclosporin A was partially reconstituted with IL-2, although no detectable IFN-gamma was produced in such cultures. In addition, IFN-gamma could not reconstitute cyclosporin-inhibited cultures. Second, inclusion of a high concentration of several distinct anti-IFN-gamma antibodies failed to inhibit MLR cultures. Third, CTL activation by stimulator cells inactivated by UV irradiation was reconstituted by IL-2, but not by IFN-gamma. These data do not support an autocrine role of IFN-gamma in CTL activation and confirm the importance of IL-2 in the primary murine MLR.
Molecular properties and regulation of mRNA expression for murine T cell-replacing factor/IL-5.
Authors: Tominaga A , Matsumoto M , Harada N , Takahashi T , Kikuchi Y , Takatsu K 
Published: December 2022

Abstract
We previously cloned cDNA for a T cell-replacing factor (TRF) that has been defined as a T cell-derived lymphokine that acts on activated B cells as a B cell growth and differentiation factor. Based on the diverse activities of rTRF on different target cells, we proposed that TRF be called IL-5. In this study, the molecular characteristics of TRF/IL-5 prepared by rDNA technology and TRF/IL-5 mRNA expression in various T cell lines and normal T cells have been studied. Specific immunoassay showed that rTRF/IL-5, which is transiently translated in vitro by rabbit reticulocyte lysate, has an apparent m.w. of 14,000. By contrast, active forms of rTRF/IL-5 translated in Xenopus oocytes has an apparent m.w. of 45,000 to 50,000 in the nonreducing condition and migrates to the m.w. of 25,000 to 30,000 under the reducing condition, indicating that active form of rTRF/IL-5 consists of dimer forms. The rTRF/IL-5 does not show detectable levels of IL-2, IL-3, and B-cell stimulatory factor 1 (IL-4) activities. Northern blot hybridization of poly (A)+ RNA from constitutively TRF-producing B151K12 T cell hybridoma revealed a single 1.7-kb band hybridizing to the cloned murine TRF/IL-5 cDNA. The expression of TRF/IL-5 mRNA in B151K12 was augmented by the stimulation with PMA plus calcium ionophore. In contrast, neither thymoma BW5147 nor IL-2-producing T cell hybridoma A55, both of which produced an undetectable level of TRF, expressed detectable levels of TRF/IL-5 mRNA. Stimulation of EL 4 and D9 cells with PMA and Con A, respectively, induced an increase in the levels of TRF/IL-5 mRNA expression accompanied by TRF/IL-5 production, whereas both cell lines did not show significant gene expression in the absence of the stimulation. In spleen cells from Mycobacterium tuberculosis-primed mice, significant expression of TRF/IL-5 mRNA was detected only when the cells were stimulated with relevant Ag, PPD. Normal spleen cells stimulated with Con A showed a significant, but approximately four-fold less expression of TRF/IL-5 mRNA. Molecular and functional properties of TRF/IL-5 will be discussed.
Electrostatic properties of cryoimmunoglobulins.
Authors: Lawson E Q , Brandau D T , Trautman P A , Middaugh C R 
Published: December 2022

Abstract
Inhibition of the cryoprecipitation of cryoimmunoglobulins by neutral salts suggests that intermolecular electrostatic (charge-charge) interactions are responsible for their abnormal solution properties. To test this hypothesis, H+ titration curves and isoelectric points were measured for two monoclonal IgG cryoglobulins (Ger and Muk) and compared with four normal (cold soluble) monoclonal IgG. The cryoglobulin Ger manifested values outside the range encountered for the other proteins. The partitioning of the IgG proteins was also examined in aqueous polyethylene glycol-dextran two-phase systems in the presence of both positive and negative salt-induced electrostatic potentials across the phase interface. Both cryoglobulins were found to behave as if they were more negatively charged than the noncryoglobulins. The experiments support the hypothesis that the differences in solubility behavior of monoclonal cryoglobulin and noncryoglobulin proteins are caused by differences in the electrostatic properties of the proteins.
The immune response toward beta-adrenergic ligands and their receptors. VIII. Extensive diversity of VH and VL genes encoding anti-alprenolol antibodies.
Authors: Nahmias C , Strosberg A D , Emorine L J 
Published: December 2022

Abstract
The V region genes (VH and VL) used in the immune response of BALB/c mice to alprenolol, a synthetic beta-adrenergic ligand, were examined by Southern blot and nucleotide sequence analyses. Fourteen anti-alprenolol hybridomas utilize 10 different combinations of six Vk, one V lambda, eight VH, three JK, one J lambda, and three JH genes. In addition to the combinatorial association, somatic mutations and junctional variation of assembled genes further contribute to diversity of the anti-alprenolol response. Although differing both in length and structure, the five H-chain third complementarity-determining region analyzed contain several acidic residues. Neither V gene utilization, nor H-chain third complementarity-determining-region structure can be simply correlated with affinity of the antibodies for the ligand. The anti-alprenolol V genes were compared with the corresponding sequences of unrelated antibodies. Antibody 37A4 shares a VH gene with anti-(Glu60Ala30Tyr10)n random terpolymer and anti-nitrophenyl antibodies, and a Vk gene with two anti-oxazolone antibodies. Antibodies 14C3 and 17C1 use the same germ-line VH and Vk genes as do anti-anti-idiotypic antibodies of the (Glu60Ala30Tyr10) system. These data demonstrate the genetic diversity of the antibody response to alprenolol, and illustrate the extensive flexibility of the immune system.
Molecular cloning of the murine homologue of CD2. Homology of the molecule to its human counterpart T11.
Authors: Yagita H , Okumura K , Nakauchi H 
Published: December 2022

Abstract
In order to characterize the mouse homologue of the CD2 molecule, which has not yet been identified by immunologic means, cDNA clones putatively encoding mouse CD2 have been isolated by cross-hybridization with a cDNA probe for rat CD2. The predicted amino acid sequence of the putative mouse CD2 protein is consistent with that of a transmembrane glycoprotein, i.e., it consists of an N-terminal region of 186 amino acids bearing six potential N-glycosylation sites, a hydrophobic transmembrane segment of 25 residues, and a large cytoplasmic region of 116 amino acids rich in proline and basic residues. Comparison with the human and rat CD2 sequences clearly indicated the predicted mouse protein to be the mouse equivalent. Striking evolutionary conservations between mouse, rat, and human CD2 were found in their cytoplasmic region, suggesting a functional consequence of that segment for the physiologic role of CD2, such as signal transduction. RNA blot hybridization analysis demonstrated the expression of CD2 in T lymphocytes and in the NK cell lineage in mice. These data strongly suggest that the putative mouse CD2 molecule may perform some biologic functions in mouse T lymphocytes and NK cells as documented in humans.
B lymphoblastoid cell lines with rearranged T cell receptor beta-chain genes retain conventional B cell surface antigen and Ig expression.
Authors: Robinson M A , Kindt T J 
Published: December 2022

Abstract
Transformation of peripheral blood lymphocytes by co-incubation with EBV produces B lymphoblastoid cell lines, but rearrangement of TCR beta-chain genes was observed in three different cell lines derived from two individuals. Because rearrangement of TCR genes in B lymphocytes is considered a rare event, these B lymphoblastoid cell lines with rearranged TCR beta-genes were examined in detail to determine whether there were any additional characteristics to distinguish them from B lymphoblastoid cell lines with germ-line TCR beta-genes. All B lymphoblastoid cell lines contained rearranged Ig H and kappa L chain genes, secreted Ig, and expressed B and not T cell surface markers. Cell lines with rearranged TCR beta-genes had rearranged both IgH genes and had rearranged and subsequently deleted both kappa C region genes. Furthermore all three B lymphoblastoid cell lines with rearranged TCR beta-genes produced small amounts of Ig with lambda-L chains. Although the cellular mechanisms maintaining lineage-specific rearrangement events remain unknown, extensive Ig gene rearrangement and inefficient Ig production by B cells may be indicators of a cellular status where normally stringent lineage-specific control elements fail to function efficiently.
Antigen-induced suppression of the proliferative response of T cell clones.
Authors: Suzuki G , Kawase Y , Koyasu S , Yahara I , Kobayashi Y , Schwartz R H 
Published: December 2022

Abstract
Proliferation of Ag-specific T cell clones can be inhibited by the addition of high concentrations of Ag at the beginning of culture. Under these conditions the cells produce lymphokines and express high affinity IL-2R but fail to divide, even after the addition of exogenous IL-2. This state results from restimulation of the cells with Ag-Ia molecule complexes approximately 20 h after initiation of culture. It can be prevented by addition of either an anti-Ia or an anti-L3T4 mAb at that time, but not by cyclosporin A, and mimicked in cultures containing low concentrations of antigen by addition at that time of high Ag concentrations or normal stimulatory concentrations of Con A. These observations suggest that restimulation of activated T cell clones 20 h after their initial stimulation prevents them from dividing.