bluuebunny/crossref_metadata_2025_split huggingface dataset:
Receptor-mediated antigen delivery into macrophages. Complexing antigen to alpha 2-macroglobulin enhances presentation to T cells.
Authors: Chu C T , Pizzo S V 
Published: December 2022

Abstract
Macrophages secrete alpha 2-macroglobulin (alpha 2M), a protein that may facilitate early Ag handling. alpha 2M is able to entrap and form covalent linkages with diverse proteins during a transient proteinase-activated state. The resulting complexes are rapidly endocytosed after binding to high affinity receptors. Such a system could be capable of efficiently delivering a multitude of proteins to macrophages. We have used T hybridoma clones that respond only to hen egg lysozyme, in a MHC-restricted manner, to probe the effect of complex formation on Ag uptake and processing by murine macrophages. Radiolabeled lysozyme was internalized more rapidly and to a greater extent when bound to alpha 2M than when unbound. Macrophages pulsed with lysozyme-alpha 2M-elastase complexes required 200 to 250 times less Ag than those pulsed with free lysozyme to achieve effective presentation to T cells. Adding equimolar amounts of alpha 2M-elastase complexes, or of alpha 2M-methylamine, to free lysozyme had no effect on basal lysozyme presentation. Receptor-recognized forms of alpha 2M, but not lysozyme or BSA, competed effectively for both uptake and presentation of lysozyme-alpha 2M-elastase complexes. These results indicate that proteinase-activated alpha 2M can enhance Ag processing by carrying Ag into macrophages through a receptor-mediated process.
Production of DNP-specific/class I MHC-restricted suppressor molecules is linked to the expression of T cell receptor alpha- and beta-chain genes.
Authors: Fairchild R L , Palmer E , Moorhead J W 
Published: December 2022

Abstract
The hapten/class I MHC-specific soluble immunoregulatory molecules produced by CD8+T cells from dinitrobenzene sulfonate-primed mice express the binding specificity and serologic determinants of alpha/beta TCR. To examine the genes used to encode these soluble immunoregulatory molecules, we utilized a surface TCR expressing Ts hybridoma, which constitutively produces a DNP/Kd-specific regulatory molecule. Northern and Southern analyses indicated that MTs 79.1 cells use a V beta 8 and a V alpha 4 gene to encode the variable regions of the surface alpha/beta TCR. A panel of TCR- variants was generated by subjecting MTs 79.1 cells to gamma-irradiation. Twelve of the TCR- variants were chosen for detailed characterization. Northern blot analyses indicated the absence of the MTs 79.1 V alpha 4 chain transcript in five of the variants and the absence of the parental V beta 8 chain transcript in the other seven. Southern blot analyses demonstrated the deletion of the parental gene encoding the alpha- or beta-chain from the genome of the respective mutant. None of the 12 TCR gene deletion mutants produced the parental suppressive activity. Expression of the parental TCR beta-chain gene in one of the beta-chain gene deletion mutants reconstituted the ability to produce this activity. As with the MTs 79.1 molecule, the regulatory molecule produced by the beta-chain gene transfectant was bound by and eluted from Sepharose columns coupled with either DNP or anti-V beta 8 antibodies. These results establish a strong linkage between the suppressor molecules produced by these Ts and TCR alpha- and beta-chain gene transcription.
MHC class II limits the functional expression of endogenous superantigens in B cells.
Authors: Lund F E , Randall T D , Woodland D L , Corley R B 
Published: December 2022

Abstract
The open reading frames of the 3' long terminal repeat of mouse mammary tumor viruses (MMTV) encode superantigens. When expressed with MHC class II molecules on the surface of B cells, superantigens stimulate T cells expressing receptors with particular V beta elements. By using B cell lymphomas as model systems, we demonstrate that stimuli, including certain lymphokines (IL-2 and IL-5) and LPS, that lead to increased MMTV transcript levels in B cells did not increase functional superantigen presentation. Furthermore, stimulation of BCL1 and CH12 cells with LPS resulted in a pronounced reduction in superantigen presentation, even though MMTV transcript levels were increased. In contrast to these effects, functional superantigen expression was increased under conditions in which class II levels were increased, even when MMTV levels remained constant, indicating that the levels of newly synthesized class II are important for functional superantigen expression. These data together imply that the amount of cell surface class II limits superantigen presentation and/or that superantigens can associate only with a limited pool of class II.
Dissociation of antigen-presenting capacity of astrocytes for peptide-antigens versus superantigens.
Authors: Rott O , Tontsch U , Fleischer B 
Published: December 2022

Abstract
Although superantigens and their molecular interactions with MHC class II molecules have been well characterized recently, little is known concerning the physiological function of different types of APC in inducing superantigen-mediated T cell activation. To evaluate the potential of nonhematopoetic cells to present superantigens to T cells, we have tested astrocytes as a typical "nonprofessional" APC. Although astrocytes can express appropriate levels of MHC class II products and adhesion molecules, they turned out to be unable to mediate superantigen-driven activation of normal T lymphocytes, even in the presence of rather high concentrations of toxins. In contrast, they could properly present equimolar amounts of nominal Ag to various Ag-specific T cell lines under the same experimental conditions. Inability of astrocytes to support T cell responses to superantigens could not be overcome by addition of cytokines IL-1 and IL-6. Binding studies with class II-expressing astrocytes revealed that T cell unresponsiveness was not due to a general failure of astrocytes to bind the superantigen. Moreover, the resulting SA-class II complex was recognizable by TCR, as demonstrated by the capacity to activate IL-2 secretion in T cell hybridomas. Our results extend previous studies demonstrating marked differences of various types of APC to trigger T cell responses to superantigens and describe for the first time a dissociation of the Ag-presenting capacity for peptide-Ag vs superantigen on an accessory cell.
Insulin regulates serine/threonine phosphorylation in activated human B lymphocytes.
Authors: Valentine M A , Licciardi K A , Clark E A , Krebs E G , Meier K E 
Published: December 2022

Abstract
Activation of either dense tonsilar B lymphocytes or the B lymphoblastoid cell line T5-1 with Staphylococcus aureus, Cowan strain I, induced surface expression of insulin receptors. Addition of insulin to these activated cells resulted in subsequent phosphorylation of the B cell surface protein CD20, the functions to regulate B cell activation. The cytoplasmic domains of CD20 contain multiple serine and threonine residues, of which at least two are followed by acidic sequences typical of substrate sites favored by casein kinase II. Tryptic mapping of CD20 isolated from intact cells treated with insulin showed increased phosphorylation on peptides having similar migration to those phosphorylated by casein kinase II in vitro. Treatment of tonsilar B cells or T5-1 cells with phorbol esters or in vitro phosphorylation by purified protein kinase C did not result in phosphorylation of peptides phosphorylated by casein kinase II, suggesting that protein kinase C is not directly involved in CD20 phosphorylation in the response to insulin. Phosphorylation of CD20 cannot be triggered by insulin in resting B cells, as the insulin receptor is expressed only after entry into the G1 phase of the cell cycle. Thus, distinct regulation of activation pathways are available to resting as opposed to activated B lymphocytes.
Expression of polyamine transporter activity during B lymphocyte cell cycle progression.
Authors: DeBenedette M , Olson J W , Snow E C 
Published: December 2022

Abstract
The movement of resting B cells into the early stages of the cell cycle is accompanied by elevations in cellular polyamine levels. Our previous results indicate that part of this increase is a consequence of enhanced levels of ornithine decarboxylase activity in activated B cells. However, the levels of ornithine decarboxylase wane within 30 h post-stimulation, suggesting that B cells may acquire polyamines from an alternative source. Results in the present communication indicate that B cells initiate the transport of extracellular polyamines as they enter the G1 stage of the cell cycle. This induction of polyamine transport activity is seen after the stimulation of B cell cycle progression by both PMA and ionomycin, as well as cognate help from activated Th cells. The transport activities are energy and temperature sensitive, and can be competitively inhibited by unlabeled ligands. The results of the competition studies are compatible with the presence of at least two types of transporters, a low affinity transporter for both putrescine and spermidine, and a higher affinity transporter selective for spermidine. The results are discussed in terms of biochemical events associated with Th cell-mediated, B cell activation.
Antibodies to CD44 trigger effector functions of human T cell clones.
Authors: Galandrini R , Albi N , Tripodi G , Zarcone D , Terenzi A , Moretta A , Grossi C E , Velardi A 
Published: December 2022

Abstract
mAb against the lymphocyte homing receptor CD44/Hermes up-regulate the proliferation of human T PBL induced by anti-CD3 or anti-CD2 mAb. Moreover, certain anti-CD44 mAb can activate human resting T cells and mouse cytotoxic T cells in the absence of anti-CD3 or anti-CD2 mAb. Here, we show that anti-CD44 mAb trigger proliferation of human CD3+/CD4+ T cell clones in a fashion similar to that observed with mAb to CD3. Such an effect is IL-2-dependent, as shown by IL-2 production induced by anti-CD44 mAb and by complete inhibition of cell proliferation in the presence of anti-IL-2 antibodies or cyclosporin A. Moreover, anti-CD44 mAb trigger human cytolytic T cell clones to lyse Fc gamma-R+ P815 cells in the absence of additional stimuli. The magnitude of the cytolytic response induced by anti-CD44 mAb is comparable to that observed in the presence of anti-CD3 mAb for both CD4+ and CD8+ TCR-alpha/beta+ clones, and for V delta 1 or V delta 2 TCR-gamma/delta+ clones. By contrast, in CD3-/CD16+ NK cell clones, no cytolytic responses to anti-CD44 mAb could be observed. Granule trypsin-like esterase enzyme (granzyme) release by cytolytic T cell clones is induced by plastic-immobilized anti-CD44 mAb. Anti-CD44 mAb-triggered proliferation ([3H]thymidine incorporation) and cytotoxicity are blocked by the protein tyrosine kinase inhibitor, genestein. In addition, ligation of the CD44 molecule induces tyrosine phosphorylation of proteins identical, by molecular mass, to those phosphorylated after anti-CD3 mAb stimulation. Notably, anti-CD44 mAb does not induce tyrosine phosphorylation of a 21-kDa protein (the phosphorylated zeta-chain of the TCR molecular complex) typically observed upon anti-CD3 mAb stimulation. In conclusion, this study shows that the ligated CD44 molecule provides the necessary stimuli for a variety of T cell-mediated functions triggered via protein tyrosine kinase-dependent signal transduction pathways at least in part similar to those that follow stimulation of the CD3/TCR complex.
Superantigen-induced peripheral tolerance inhibits T cell responses to immunogenic peptides in TCR (beta-chain) transgenic mice.
Authors: Perkins D L , Wang Y , Ho S S , Wiens G R , Seidman J G , Rimm I J 
Published: December 2022

Abstract
TCR (beta-chain) transgenic mice were tolerized with the superantigen staphylococcal enterotoxin B (SEB). Three to 28 days after tolerization with SEB, flow cytometry of peripheral T cells showed the persistence of SEB-unresponsive T cells that did not express reduced levels of the TCR (beta-chain) transgene. Stimulation of the tolerized T cells with a panel of superantigens (SEC1), mitogens (Con A, PHA, and pertussis toxin) and mAb (anti-CD3 epsilon) did not induce T cell proliferation. In contrast to other models, exogenous rIL-2 did not reverse unresponsiveness and induce proliferation. In addition, lymphokines rIL-4 and rIL-6 also did not induce proliferation. However, the unresponsive T cells did respond to the combination of PMA plus ionomycin, but not to PMA or ionomycin alone. Thus, the block in signal transduction in the anergic state occurs between the stimulation of cell surface receptors and the activation of protein kinase C and the increase in intracellular calcium. In addition, these results show that mature T cells tolerized with the superantigen SEB are unresponsive to a wide array of T cell stimuli, indicating a block in a common signal transduction pathway.
Induction of activation-driven death (apoptosis) in activated but not resting peripheral blood T cells.
Authors: Wesselborg S , Janssen O , Kabelitz D 
Published: December 2022

Abstract
Signaling via the CD3/TCR complex induces programmed cell death (apoptosis) in immature thymocytes and transformed T lymphocytes (hybridomas or leukemic cells). Accumulating evidence indicates, however, that apoptosis can be triggered also in mature peripheral T cells. Here we show that a significant fraction of cells of a given IL-2-dependent TCR-alpha beta + clone or polyclonal short term line is killed when cultured for 20 h in the presence of PHA, anti-CD3 (OKT3), or anti-TCR (BMA031) mAb. Apoptosis can be triggered by these stimuli in CD4+, CD8+, and CD4-CD8- (double-negative) TCR-alpha beta+ clones. Activation-driven cell death (as quantified by propidium iodide staining and FACS analysis) is associated with fragmentation of DNA into oligonucleosomal bands of approximately 200 bp. Although freshly isolated peripheral blood T cells are largely resistant to apoptosis, the sensitivity to anti-CD3/TCR mAb or PHA-triggered cell death gradually increases upon activation and IL-2-dependent culture of T cells, and reaches a plateau level after 15 to 20 days. These data indicate that stimuli that activate resting T cells initiate death by apoptosis in activated T cells. The implications of these results for the regulation of cellular immune responses and the establishment of peripheral tolerance will be discussed.
Regulated expression of germline antigen receptor genes in mast cell lines from the murine embryo.
Authors: Siden E J 
Published: December 2022

Abstract
Abelson murine leukemia virus-transformed cell lines derived from the earliest period of murine embryonic hematopoiesis express multiple characteristics of immature mast cells. We show here that both Ig and TCR-gamma genes are transcribed in some of these embryo-derived mast cell lines. Germline H chain V region transcripts are expressed constitutively, and germline Ig-mu and TCR-gamma constant region gene transcripts are induced in culture by the antiproliferative drug, BUdR. Coordinate with the up-regulation of the receptor gene transcripts, the B cell surface protein, B220, and IL-4 mRNA are also induced. The mechanism of action of BUdR was revealed by the observation that exogenous IL-4 alone induced both mu- and TCR transcripts in the transformed cells. Nontransformed mast cells cultured from embryonic liver and placenta also contain mu- and TCR-gamma transcripts. The expression of multiple Ag receptor genes in mast cells suggests that this cell type may be useful for our understanding of some of the early events of lymphoid development.
Nonimmunogenic tumor cells may efficiently restimulate tumor antigen-specific cytotoxic T cells.
Authors: Kündig T M , Bachmann M F , Lefrancois L , Puddington L , Hengartner H , Zinkernagel R M 
Published: December 2022

Abstract
Induction of immunity to a viral protein that had been transfected into a tumor cell line was studied. The nucleoprotein (NP) of vesicular stomatitis virus (VSV) was used as a model tumor-associated Ag after transfection into EL-4, and H-2b thymoma originating from C57BL/6 mice. The NP-transfected cell line (EL-4NP) was lysed by NP-specific CTL and was found to restimulate NP-specific CTL in vitro as efficiently as did VSV-infected macrophages. Despite both of these in vitro characteristics, C57BL/6 mice inoculated with EL-4NP did not mount a measurable NP-specific CTL response and developed a lethal tumor as rapidly as did mice given control EL-4. This lack of immunogenicity could not be explained by down-regulation of MHC class I molecules or by loss of NP; even EL-4NP cells metastasizing to the spleen kept their high restimulatory capacity and excellent target characteristics. However, once mice were immunized with VSV or with a vaccinia-VSV-NP recombinant virus they were protected against tumor growth of EL-4NP by CD8+ CTL but not by CD4+ T cells. Taken together, the failure of the tumor-associated Ag to induce a protective T cell response in vivo despite its excellent capacity to restimulate CTL in vitro may encourage adjuvant immunotherapy in cancer; even the effects of weakly immunizing tumor vaccines, e.g., recombinant viruses, may be efficiently amplified by tumor cells.
Blocking lymphoma invasiveness with a monoclonal antibody directed against the beta-chain of the leukocyte adhesion molecule (CD18).
Authors: Zahalka M A , Okon E , Naor D 
Published: December 2022

Abstract
The same integrin adhesion molecules used by normal leukocytes for traffic and localization in inflammation sites may be used by malignant cells for dissemination. Identifying the adhesion molecules and then blocking them with appropriate antibody may therefore prove useful for controlling tumor spread. This prediction was tested on a spontaneous murine T cell lymphoma (LB) that expresses LFA-1 adhesion molecules. The adhesion molecules were identified by fluorocytometry and immunoprecipitation with anti-CD18 mAb (M18/2). Subcutaneously inoculated LB lymphoma rapidly infiltrated the spleen and the lymph nodes, as indicated by histologic examination and [3H]thymidine incorporation assay of proliferating LB cells derived from the invaded organs. The normal organization of the lymphoid organs was totally effaced by the infiltrating LB cells. Intravenous injection of anti-CD18 mAb, protein G-purified anti-CD18 mAb, or its F(ab')2 fragments (but not irrelevant control mAb) blocked the invasion of the s.c. inoculated lymphoma into the spleen. Whereas i.v. injected anti-CD18 mAb could not block the infiltration of LB cells into the lymph nodes, local s.c. injection of this antibody near the lymph nodes partially inhibited lymphoma invasion into these organs. It was further found that LB cells form aggregates with spleen cells but not with lymph node cells. In addition, spleen-infiltrating LB cells invade both the spleen and the lymph nodes after s.c. injection. On the other hand, lymph node-infiltrating LB cells invade mainly the lymph nodes under similar circumstances.
MCP-1 expression by rat type II alveolar epithelial cells in primary culture.
Authors: Paine R , Rolfe M W , Standiford T J , Burdick M D , Rollins B J , Strieter R M 
Published: December 2022

Abstract
Recruitment and activation of mononuclear phagocytes are potentially critical regulatory events for control of pulmonary inflammation. Located at the boundary between the alveolar airspace and the interstitium, alveolar epithelial cells are ideally situated to regulate the recruitment and activation of mononuclear phagocytes through the production of cytokines in response to inflammatory stimulation from the alveolar space. To test this hypothesis, we investigated the production of monocyte chemotactic polypeptide-1 (MCP-1), a protein that is chemotactic for and that activates monocytes, by rat type II alveolar epithelial cells in primary culture. Immunocytochemical staining using anti-murine JE, an antibody recognizing rat MCP-1, demonstrated cell-associated MCP-1 Ag throughout the monolayer. The intensity of staining was increased in response to IL-1 beta. When type II epithelial cells formed a tight monolayer on a filter support, there was polar secretion of MCP-1 Ag into the apical compartment by both control and IL-1-stimulated cells as measured by specific MCP-1 ELISA. Northern blot analysis revealed that IL-1 and TNF-alpha stimulated MCP-1 mRNA expression in a dose-dependent manner, whereas dexamethasone blocked MCP-1 expression by cells stimulated with IL-1. In contrast to previous results using transformed epithelial cell lines, MCP-1 mRNA was induced in these primary cultures directly by stimulation with LPS. These data suggest that alveolar epithelial cells may have an important and previously unrecognized role in the initiation and maintenance of inflammatory processes in the lung by recruiting and activating circulating monocytes through the production of MCP-1.
Cyclosporin H is a potent and selective formyl peptide receptor antagonist. Comparison with N-t-butoxycarbonyl-L-phenylalanyl-L-leucyl-L-phenylalanyl-L- leucyl-L-phenylalanine and cyclosporins A, B, C, D, and E.
Authors: Wenzel-Seifert K , Seifert R 
Published: December 2022

Abstract
The cyclic undecapeptide, cyclosporin (Cs) H, is a potent inhibitor of FMLP-induced superoxide anion (O2-) formation in human neutrophils. We studied the effects of CsH in comparison with those of N-t-butoxycarbonyl-L-phenylalanyl-L-leucyl-L-phenylalanyl-L-leucyl-L- phenylalanine (BocPLPLP), a well known formyl peptide receptor antagonist, and of other Cs on activation of N6,2'-O-dibutyryl adenosine 3:5'-monophosphate-differentiated HL-60 cells and human erythroleukemia cells (HEL cells). CsH inhibited FMLP binding in HL-60 membranes with a Ki (inhibition constant) of 0.10 microM. CsH inhibited activation by FMLP of high affinity GTPase (the enzymatic activity of alpha-subunits of heterotrimeric regulatory guanine nucleotide-binding proteins) in HL-60 membranes with a Ki of 0.79 microM. CsH inhibited the stimulatory effects of FMLP on cytosolic Ca2+ concentration ([Ca2+]i), O2- formation, and beta-glucuronidase release with Ki values of 0.08, 0.24, and 0.45 microM, respectively. BocPLPLP was 14-fold less potent than CsH in inhibiting FMLP binding and 4- to 6-fold less potent than CsH in inhibiting FMLP-induced GTP hydrolysis, rises in [Ca2+]i, O2- formation, and beta-glucuronidase release. CsA reduced FMLP-induced O2- formation by 20%, but CsB, CsC, CsD, and CsE did not. CsA, CsB, CsC, CsD, and CsE did not affect FMLP-induced rises in [Ca2+]i. BocPLPLP inhibited leukotriene B4-induced rises in [Ca2+]i with a Ki of 0.33 microM, whereas CsH showed no inhibitory effect. CsH and BocPLPLP did not inhibit the rises in [Ca2+]i induced by several other stimuli in HL-60 cells and HEL cells. Our results show that 1) CsH is a more potent formyl peptide receptor antagonist than BocPLPLP; 2) unlike BocPLPLP, CsH is selective; and 3) N-methyl-D-valine which is present at position 11 of the amino acid sequence of CsH but not of other Cs is crucial for FMLP antagonism.