bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lymphocytes from SJL/J mice immunized with spinal cord respond selectively to a peptide of proteolipid protein and transfer relapsing demyelinating experimental autoimmune encephalomyelitis.
Authors: Whitham R H , Bourdette D N , Hashim G A , Herndon R M , Ilg R C , Vandenbark A A , Offner H 
Published: December 2022

Abstract
Relapsing experimental autoimmune encephalomyelitis (R-EAE) can be induced in SJL/J mice by immunization with spinal cord homogenate and adjuvant. The specific Ag(s) responsible for acute disease and subsequent relapses in this model is unknown. Myelin basic protein (BP), an encephalitogenic peptide of BP (BP 87-99), and proteolipid protein (PLP) can each induce R-EAE in SJL/J mice, and a peptide of PLP (PLP 139-151) has been reported to induce acute EAE. To determine the encephalitogens in cord-immunized mice with R-EAE, the in vitro proliferative responses of lymph node cells (LNC) and central nervous system mononuclear cells to BP, BP peptides, and PLP peptides were examined during acute EAE and during relapses. LNC responded only to PLP peptides 139-151 and 141-151 and did not respond to BP or its peptides during acute or chronic disease. Central nervous system mononuclear cells also preferentially responded to PLP 139-151 and 141-151 during acute and relapsing disease. A PLP 139-151 peptide-specific Th cell line was selected from LNC of cord-immunized donors. Five million peptide-specific line cells transferred severe relapsing demyelinating EAE to naive recipients. We conclude that PLP peptide 139-151 is the major encephalitogen for R-EAE in cord-immunized SJL/J mice. We demonstrate for the first time that Th cells specific for this peptide are sufficient to transfer relapsing demyelinating EAE. The predominance of a PLP immune response rather than a BP response in SJL/J mice suggests that genetic background may determine the predominant myelin Ag response in human demyelinating diseases such as multiple sclerosis.
IFN-gamma induces the expression of the genes for MHC class II I-A beta and tumor necrosis factor through a protein kinase C-independent pathway.
Authors: Celada A , Maki R A 
Published: December 2022

Abstract
The mechanism of gene expression for the MHC I-A beta and TNF genes was studied in murine bone marrow macrophages. The treatment of macrophages with PMA stimulated the expression of TNF, but not I-A beta, suggesting that the TNF gene is responsive to activators of protein kinase C whereas the I-A beta gene is not. The treatment of macrophages with IFN-gamma led to an increase in the level of RNA for both TNF and I-A beta. The increase in expression of I-A beta and TNF, induced by IFN-gamma, was blocked by naphthalenesulfonamide or phenothiazine (trifluoperazine) but was not affected by the addition of isoquinolinesulfonamide or sphingosine. These results suggest that the induced expression of I-A beta and TNF by IFN-gamma is mediated by a pathway that is protein kinase C independent. This was supported by the finding that calcium ionophores were also able to induce the gene expression of both TNF and I-A beta. We observed that when both IFN-gamma and PMA were added to the macrophages, the level of RNA for TNF increased to a higher level than the level seen when either agent alone was added to the cells. In contrast, the addition of both IFN-gamma and PMA to macrophages had an inhibitory effect on the expression of the I-A beta gene. These results further emphasize the complex nature of gene regulation during the activation of macrophages.
IL-1 signal transduction pathways. I. Two functional IL-1 receptors are expressed in T cells.
Authors: Muñoz E , Zubiaga A M , Sims J E , Huber B T 
Published: December 2022

Abstract
We have recently characterized a subline of the Th2 cell line D10.G4.1, D10A, which responds to exogenous IL-1 in the absence of cofactors. In this cell line IL-1 activates two distinct transmission signal pathways, one leading to increased levels of intracellular cAMP, and the other to the phosphorylation of an 80-kDa substrate of protein kinase C (PKC). To determine whether both pathways are activated upon occupancy of a single IL-1R, we used a mAb, M15, which blocks binding of IL-1 to the 80-kDa IL-1R, known to be expressed in Th2 cells. Whereas M15 was able to inhibit the accumulation of cAMP induced by IL-1, it had no effect on the IL-1-induced phosphorylation of the 80-kDa substrate of PKC or the c-fos mRNA expression. In addition, we show that IL-1 induces the expression of the two proto-oncogenes c-myb and c-myc through the 80-kDa IL-1R, and that this induction is PKC independent. The proliferation of D10A cells in response to IL-1 is blocked by M15, but is unaffected by H-7, a potent inhibitor of PKC. These results indicate that the IL-1-induced proliferation of D10A cells is independent of PKC. In addition, IL-1 induces c-fos mRNA expression in thymocytes but not in EL-4 cells.
IL-6 and IL-1 enhance the accessory activity of human blood monocytes during differentiation to macrophages.
Authors: Ruppert J , Peters J H 
Published: December 2022

Abstract
The role of IL-6 and IL-1 in the regulation of accessory activity and differentiation in the human monocyte/macrophage (Mo/Mph) system was investigated. IL-6 combined with IL-1 had a strong effect on the accessory activity of Mo-derived cells dependent on their state of differentiation in vitro. Fresh Mo prepared from peripheral blood differentiated into potent accessory cells in vitro within 24 h in the absence of exogenous triggers in serum-containing and serum-free medium. Mo cultured for 2 days in the presence of the cytokines IL-6 and IL-1 did not significantly increase their spontaneous accessory activity. However, the simultaneous addition of antibodies against IL-6 and IL-1 to accessory Mo cultures significantly diminished their T cell stimulatory capacity. These findings suggest an important positive feedback role of IL-6 and IL-1, secreted by Mo at this early state of differentiation. In marked contrast, untreated mature Mph generated in vitro from Mo exhibited a low spontaneous accessory potency. However, when these cells were subjected to IL-6 and/or IL-1, we observed a strong dose dependent increase in their potency to stimulate a T cell response. Parameters indicating the differentiation of Mo to Mph, such as acid phosphatase and 5' nucleotidase, were not influenced by the addition of IL-1, IL-6, or a mixture of both and confirmed the presence of mature Mph after 6 days of culture. Based on these observations, we conclude that the monocyte-derived cytokines IL-6 and IL-1 not only directly act on T cells but may also function as a signal for accessory activity during Mo/Mph differentiation.
Differences in the tumor necrosis factor-alpha-mediated lysis by fixed natural cytotoxic cells and fixed cytotoxic macrophages.
Authors: Vanderslice W E , Collins J L 
Published: December 2022

Abstract
TNF-alpha has been shown to be associated with macrophage cell membranes in such a way as to retain cytolytic activity despite fixation of the macrophage effector cells with paraformaldehyde. In this paper we report that, similar to cytotoxic macrophages, natural cytotoxic (NC) cells also use cell-associated TNF to lyse sensitive target cells. However, in contrast to fixed cytotoxic macrophages, NC cells do not retain cytolytic activity after fixation with paraformaldehyde. Additionally, the cytolytic activity of paraformaldehyde-fixed NC cells is not increased by incubation with LPS or by incubation with rTNF before fixation. Western blot analysis indicates that, unlike macrophages, NC cells use a smaller (17 kDa) constitutively active form of TNF. These results indicate that, although both macrophages and NC cells use effector cell-associated TNF to mediate lysis of sensitive targets, the way in which TNF is associated with these two types of effector cells must be different.
Ig H and L chain contributions to autoimmune specificities.
Authors: Radic M Z , Mascelli M A , Erikson J , Shan H , Weigert M 
Published: December 2022

Abstract
An Ig H chain expression vector has been constructed by using the V region of 3H9, an antibody that binds ssDNA, dsDNA, and cardiolipin. The H chain construct was transfected into six hybridoma cell lines expressing Ig L chains. All resulting H and L chain combinations had at least some affinity for ssDNA, whereas five also bound dsDNA to a similar degree as 3H9. The loss of dsDNA binding was correlated with a single amino acid difference between two V kappa 8 L chains. A further characteristic of 3H9, its immunofluorescent staining pattern, was shared by four of the recombinant antibodies, whereas its specificity for cardiolipin was shared with five. The transfections reported here show that a V kappa 3 L chain confers specificity for an RNA-associated epitope and that a V kappa 21E L chain prevents cardiolipin binding. These experiments suggest that the 3H9 H chain contributes essential determinants required for binding to DNA as well as cardiolipin but that L chains can modulate or prevent this binding. L chains may also expand the specificity of a recombinant antibody.
Tyrosine phosphorylation of the Fc gamma RIII(CD16): zeta complex in human natural killer cells. Induction by antibody-dependent cytotoxicity but not by natural killing.
Authors: Vivier E , Morin P , O'Brien C , Druker B , Schlossman S F , Anderson P 
Published: December 2022

Abstract
NK cells are large granular lymphocytes capable of killing certain tumor cells and virally infected cells in a non-MHC-restricted manner. NK cells can also effect an antibody dependent cytotoxicity that is triggered by CD16, an FcR for IgG. In NK cells, CD16 is expressed in association with zeta, a signal transducing subunit of the TCR complex. Here we show that, just as T cell activation via the TCR complex results in tyrosine phosphorylation of zeta TCR, NK cell activation via CD16 results in tyrosine phosphorylation of zeta NK. Whereas antibody-dependent cytotoxicity also results in tyrosine phosphorylation of zeta, natural cytotoxicity does not. Our results indicate that zeta functions as a transducing element for antibody dependent, but not antibody independent killing by NK cells. Consequently, NK cells are likely to express at least two distinct receptor complexes capable of triggering cytolytic effector function.
The mast cell-committed progenitor. In vitro generation of committed progenitors from bone marrow.
Authors: Ashman R I , Jarboe D L , Conrad D H , Huff T F 
Published: December 2022

Abstract
Mast cell-committed progenitors are detected in the unique microenvironment of the mesenteric lymph node (MLN) of Nippostrongylus brasiliensis-infected mice but not in naive bone marrow. We have determined that MLN cells, after infection, produce high levels of IL-3, IL-4, and IgE, presumably in the form of immune complexes with antigens produced by the infecting helminth. After N. brasiliensis infection, peak production of these factors occurs several days before the peak appearance of mast cell-committed progenitors in the MLN. To determine if these factors play a role in mast cell commitment, we recreated these conditions, in vitro. Naive bone marrow cells were cultured with combinations of IL-3, IL-4, and IgE immune complexes, or on IgE-coated plates, and then assayed for acquisition of the ability to form mast cell colonies when supplemented with fibroblast-conditioned medium alone. IL-3 and IgE immune complexes, and, unexpectedly, IgE immune complexes alone were found to be capable of producing mast cell-committed progenitors, i.e., cells responsive to fibroblast-conditioned medium alone, from bone marrow, whereas IL-4 did not enhance production of mast cell-committed progenitors from bone marrow. Production of IFN-gamma peaked at the same time point as committed progenitor activity and may be responsible for down regulating the response.
Natural killer cell-dependent mycobacteriostatic and mycobactericidal activity in human macrophages.
Authors: Bermudez L E , Young L S 
Published: December 2022

Abstract
Host defense mechanisms against Mycobacterium avium complex (MAC) are poorly understood. Recent evidence suggests the role of NK cells in the host defense against some intracellular pathogens. We investigated whether NK cells play a role in MAC infection. IL-2-activated human NK cells were incubated with human monocyte-derived macrophages either before or after infection with MAC. Macrophages were lysed 3 and 5 days after infection for quantitation of viable intracellular organisms. Although no killing was observed by nonstimulated macrophages, exposure to IL-2-treated NK cells for 24 h before infection induced macrophage to kill 70 +/- 8% of intracellular MAC by 3 days, and 81% +/- 4% in 5 days (p less than 0.01 for both compared with control). Killing was not blocked by incubation with anti-TNF antibody (Ab) or anti-IFN-gamma Ab. Similarly, incubation of macrophages for 24 h with supernatant obtained from IL-2 activated NK cells was associated with 74 +/- 4% killing of intracellular MAC in 3 days and 81 +/- 6% in 5 days (p less than 0.01 for both compared with control). However, the supernatant-mediated activation was partially blocked by anti-TNF Ab (46 +/- 6%; p less than 0.05) but not by anti-IFN gamma Ab. When infected macrophages were incubated with NK cells 24 h after infection for 48 h, they killed 54 +/- 3% of intracellular M. avium in 3 days and 73 +/- 5% in 5 days (p less than 0.02 for both compared with control). This effect was also not blocked by either anti-TNF or anti-IFN gamma Ab. These results suggest that activated NK cells may have an important role in the intracellular killing of MAC and that the NK-mediated activation of macrophages is in part mediated by TNF.
Synergistic role of CD4+ and CD8+ T lymphocytes in IFN-gamma production and protective immunity induced by an attenuated Toxoplasma gondii vaccine.
Authors: Gazzinelli R T , Hakim F T , Hieny S , Shearer G M , Sher A 
Published: December 2022

Abstract
BALB/c mice vaccinated with a temperature-sensitive mutant (TS-4) of Toxoplasma gondii develop complete resistance to lethal challenge with a highly virulent toxoplasma strain (RH). This immunity is known to be dependent on IFN-gamma synthesis. In vitro and in vivo T cell depletions were performed in order to identify the subsets responsible for both protective immunity and IFN-gamma production. When stimulated with crude tachyzoite Ag in vitro, CD4+ cells from vaccinated mice produced high levels of TH1 cytokines (IL-2 and IFN-gamma) but not TH2 cytokines (IL-4 and IL-5). CD8+ cells, in contrast, produced less IFN-gamma and no detectable IL-2. Nevertheless, they could be induced to synthesize IFN-gamma when exposed in culture to exogenous IL-2. In vivo treatment with anti-CD4 plus anti-CD8 or anti-IFN-gamma antibodies during challenge infection completely abrogated resistance to T. gondii. In contrast, treatment with anti-CD4 alone failed to reduce immunity, whereas anti-CD8 treatment partially decreased vaccine-induced resistance. These results suggest that although IFN-gamma and IL-2-producing CD4+ lymphocytes are induced by vaccination, IFN-gamma-producing CD8+ T cells are the major effectors of immunity in vivo. Nevertheless, CD4+ lymphocytes appear to play a synergistic role in vaccine-induced immunity, probably through the augmentation of IFN-gamma synthesis by the CD8+ effector cells. This hypothesis is supported by the observation that when giving during vaccination, as opposed to after challenge, anti-CD4 antibodies are capable of blocking protective immunity.
Entry of antivirally active T lymphocytes into the thymus of virus-infected mice.
Authors: Gossmann J , Löhler J , Lehmann-Grube F 
Published: December 2022

Abstract
The thymus has long been regarded as an immunologically "privileged site" by being shielded against the entry of exogenous Ag as well as protective elements of the immune system. After i.p. infection of mice, the lymphocytic choriomeningitis virus multiplied in this organ. Viral Ag was found predominantly in the epithelial-reticular cells of the medulla and to a lesser extent in such cells of the cortex. Beginning on day 7 after infection, the virus disappeared, a process that could be blocked by depleting the mice of peripheral T lymphocytes or of CD8+ cytotoxic T lymphocytes. Viral clearance was accelerated by i.v. injection of splenocytes from mice, which themselves were just eliminating the virus. CD8+ cells from CD8-congenic donor mice, most with blast morphology, were detected immunocytochemically in the thymus, predominantly in the medulla. A few CD8+ T lymphocytes from donors not previously infected were also demonstrated in the thymic tissue of infected mice. Our findings indicate that the lymphocytic choriomeningitis virus has access to the thymus and suggest that it is cleared by the antiviral activity of circulating cytotoxic T lymphocytes. Thus, just as other organs, the thymus appears to be subject to immune surveillance by mature T lymphocytes that have their origin in secondary lymphoid tissues.
Human natural killer cells express VLA-4 and VLA-5, which mediate their adhesion to fibronectin.
Authors: Gismondi A , Morrone S , Humphries M J , Piccoli M , Frati L , Santoni A 
Published: December 2022

Abstract
Very late Ag (VLA)-3, VLA-4, and VLA-5, belonging to the beta-1 subfamily of integrins, have been recently identified as receptors for different binding regions of fibronectin (FN). We have detected VLA-4 and VLA-5, but not VLA-3, on fresh CD3-, CD16+, CD56+ human NK cells by flow cytometry and immunochemical analyses using mAb directed against beta-1, alpha-3, alpha-4, and alpha-5 subunits. Binding assays, performed on FN-coated plates, showed that NK cells specifically adhere to FN and their binding capacity is increased by MgCl2 but not by CaCl2. Using as inhibitory probes a polyclonal antibody against the beta-1 chain of the human FN receptor, the synthetic peptide GRGDSP, which is able to inhibit cellular adhesion mediated by VLA-5, the CS1 fragment, which contains the principal adhesion site in the IIICS domain recognized by VLA-4, and functional mAb directed against alpha-4 or alpha-5 subunits, we show that both VLA-4 and VLA-5 mediate the adhesion of human NK cells to FN. The expression of these integrin receptors may be relevant for NK interaction with extracellular matrix components and other cell types.
Induction of human T cell proliferation by a monoclonal antibody to CD5.
Authors: Spertini F , Stohl W , Ramesh N , Moody C , Geha R S 
Published: December 2022

Abstract
A mouse mAb, TS 43, which recognized the human CD5 molecule, was found to induce the proliferation of human peripheral blood T cells. TS 43 mAb precipitated from 125I-radiolabeled T cells a 67-kDa band, which comigrated with the 67-kDa band precipitated by the anti-CD5 mAb OKT1. Preclearing of cell lysates with OKT1 mAb abolished the capacity of TS 43 mAb to precipitate radiolabeled material from T cell lysates. Furthermore, a mouse T cell hybridoma transfected with human CD5 was stained by TS 43 mAb. T cell proliferation mediated by TS 43 mAb was monocyte dependent, and was accompanied by IL-2R expression and by IL-2 synthesis. T cell activation by TS 43 mAb involved a rise in intracellular calcium level (CA2+)i and was dependent on the expression of the TCR/CD3 complex because no rise in (Ca2+)i was observed in a TCR-beta-deficient Jurkat T cell mutant. This study indicates that CD5 should be added to the list of surface molecules that can signal T cells to proliferate.
IFN-gamma inhibits inflammatory cell recruitment and the evolution of bacterial cell wall-induced arthritis.
Authors: Wahl S M , Allen J B , Ohura K , Chenoweth D E , Hand A R 
Published: December 2022

Abstract
Localization of streptococcal cell wall Ag (SCW) in the synovial tissue of treated rats induces an influx of leukocytes and a cell-mediated immune response leading to arthritis and joint destruction. Systemic administration of the T cell product, IFN-gamma (10(6) U/kg/day), suppresses the recruitment of leukocytes into the synovium and effectively inhibits the inflammation and pathology characteristic of SCW-induced arthritis (articular index 10.4 +/- 0.6 for SCW vs 2.0 +/- 0.7 for SCW with IFN-gamma, p less than 0.005). Monocyte-macrophages from animals treated with IFN-gamma exhibited defective chemotactic responses when tested in vitro and furthermore, monocytes cultured with IFN-gamma (25 to 500 U/ml) in vitro had significantly suppressed chemotactic responses to the complement fragment C5a (p less than 0.005). The decreased ability to migrate to C5a was associated with decreased binding of fluorochrome-conjugated C5a indicative of reduced expression of C5a receptors. Based on these data, IFN-gamma that induces monocyte maturation as reflected by increased Ia expression conversely inhibits C5a receptor expression. Although locally elevated IFN-gamma levels may serve to inhibit recruitment away from an inflammatory site, systemic exposure to IFN-gamma appears to inhibit leukocyte recruitment to the inflammatory site by its ability to induce premature maturation and concomitant inability to respond to certain chemotactic ligands. Inasmuch as monocyte recruitment to the synovium is pivotal in the development of SCW-induced polyarthritis, the ability of IFN-gamma to inhibit this event effectively inhibits the synovial pathology.
Generation of lymphokine-activated killer activity in T cells. Possible regulatory circuits.
Authors: Geller R L , Smyth M J , Strobl S L , Bach F H , Ruscetti F W , Longo D L , Ochoa A C 
Published: December 2022

Abstract
CD4+ and CD8+ T cells do not develop significant lymphokine-activated killer (LAK) activity when PBL are cultured with IL-2 or even when they are activated with a T cell stimulus such as OKT3 mAb. The possibility that a T cell regulatory mechanism prevents the development of LAK activity by CD4+ or CD8+ cells in OKT3 mAb and IL-2 cultures was tested by depleting CD8+ or CD4+ cells from PBL before stimulation with OKT3 and IL-2. Under these conditions, the remaining CD4+ and CD8+ cells were able to generate non-MHC-restricted lysis of NK-resistant tumor targets. Our data suggested that a regulatory signal was present in the culture to prevent the development of lytic function by T cells. T cells removed from the PBL cultures were, upon culture with IL-2, able to generate high LAK activity, suggesting that inhibition of the CD4+ or CD8+ T cell-mediated LAK activity was an active ongoing process, which blocked the lysis at the level of the activated cell and not the precursor cell. Mixing experiments demonstrated that the CD4+ or the CD8+ cells isolated from the PBL cultures were able to inhibit the development of lytic function in the CD4-depleted and CD8-depleted cultures. Transforming growth factor-beta (TGF-beta) has been shown to block LAK activity of NK cells in IL-2-stimulated cultures. When TGF-beta was added to CD4(+)- or CD8(+)-depleted cultures, it also inhibited LAK activity of T cells in a dose-dependent fashion, without interfering with T cell growth. Lytic activity returned to activated levels when TGF-beta was removed from the culture medium, thereby demonstrating the reversibility of TGF-beta inhibition.