Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of cell contact in T-dependent B cell activation was examined. Small resting B cells from C57BL/6 mice were cultured with CBA-derived, non-alloreactive cloned T helper cells in anti-T cell receptor V beta 8-coated microwells. This induced polyclonal B cell activation to enter cell cycle (as measured by thymidine incorporation at 2 days) and to secrete immunoglobulin (as measured by an enzyme-linked immunoassay detecting high-rate Ig secretion at 5 days). The inclusion of monoclonal antibodies against LFA-1. ICAM-1 and CD4 in these cultures strongly inhibited antibody responses, although proliferative responses were only inhibited to about 50%. Inhibitory monoclonal antibodies did not significantly affect lipopolysaccharide-induced responses. T cell activation to interleukin (IL) 3 secretion, nor did they inhibit the formation of multicellular clusters containing T and B cells. There was no correlation between the level of expression of adhesion molecules by T cells and their ability to induce B cell responses. Anti-LFA-1 abrogated T-dependent responses to IL2 which were inducible after 2 days in culture, but did not inhibit the induction of this IL2 responsiveness. These results suggest that continued cell contact involving adhesion/accessory molecules induces B cells to proliferate and to respond to T cell lymphokines. A signaling role for cell interaction molecules on B cells is proposed, similar to the role of these and analogous molecules on T cells.
 ...
PMID:A role for adhesion molecules in contact-dependent T help for B cells. 167 35

In this report we have analyzed the effect of recombinant interleukin 2 (rIL 2) and rIL 2-activated natural killer (NK) cells on the production of immunoglobulin isotypes by lipopolysaccharide (LPS)-stimulated spleen cells from nude mice. We found that rIL 2 induced a dose-dependent increase of IgG2a secretion and a concomitant inhibition of the secretion of other Ig isotypes. The analysis of the phenotype of LPS- and LPS+ rIL 2-stimulated nude spleen cells showed the appearance of a Thy-1+ asialo GM-1+slgM-CD3-CD4-CD8- cell population in the presence of rIL 2. A population with a similar phenotype was generated upon stimulation of spleen cells from nude mice with rIL 2 alone. These cells lysed YAC-1 cells, did not contain the alpha or gamma transcripts encoding the corresponding T cell receptor chains and are therefore NK cells activated by rIL 2. In co-culture experiments, these cells selectively increased the secretion of IgG2a by LPS-stimulated splenocytes from nude mice. The IgG2a induction triggered by rIL 2-activated NK cells, as well as that triggered by rIL 2, were blocked by an anti-interferon gamma monoclonal antibody. Thus, rIL 2 activated-NK cells enhance the production of IgG2a by secreting interferon-gamma.
 ...
PMID:Recombinant interleukin 2-activated natural killer cells regulate IgG2a production. 169 33

We examined whether bacterial lipopolysaccharide, at a dose range extending to less than 1.0 ng/ml, would work with cofactors to induce MHC-nonrestricted cytotoxic cells. To this end, normal mouse splenocytes were cultured for 5 days with LPS and potential cofactors, after which the cells were tested for cytotoxic activity in short-term 51Cr-release assays. We found that LPS can act synergistically with the macromolecular polyanions, dextran sulfate and polyinosinic acid. The effector cells induced by LPS and polyanions showed characteristics of activated NK cells in that they were (1) cytotoxic for widely differing sources of tumor cells, (2) not inhibited by an anti-T cell receptor antibody, and (3) not removed by depletion of CD4+ or CD8+ cells. LPS was active at picogram concentrations when dextran sulfate was included. Exposure of splenocytes to LPS was necessary during the early phase of the 5-day culture, but as little as 1 h of exposure was required, whereas exposure to the macromolecular polyanions during either the first or the last 2 days of a 5-day culture with LPS was effective. As expected with LPS activity, the cytotoxic cell response was prevented by polymyxin B or by the use of splenocytes from LPS non-responder C3H/HeJ mice. Screening of the S. minnesota R mutants and other partial LPS structures revealed that lipid A was closely associated with LPS activity in this assay system and that at least one partially detoxified structure, a deacylated LPS, could substitute for native LPS.
 ...
PMID:Bacterial lipopolysaccharide acts synergistically with selected macromolecular polyanions to induce MHC-nonrestricted cytotoxic cells. 191 77

HLA-DQw6 transgenic C57BL/6 mice (DQw6-B6) were utilized to define the role of HLA-DQw6 gene product in immune-recognition. To investigate the responsiveness of lymph node cells from C57BL/6 mice (B6) or DQw6-B6 in response to DQw6 molecules expressed in the DQw6-B6, in vitro secondary MLR was performed. The lymph node cells from B6 proliferated in response to spleen cells from DQw6-B6, whereas those from DQw6-B6 did not. These results suggested that DQw6-B6 acquired tolerance to DQw6 molecules. The difference of T cell repertoire between B6 and DQw6-B6 was investigated using mAbs directed against T cell receptor V beta regions, V beta 3, V beta 5, V beta 6, V beta 8, V beta 11 and V alpha 3.2. Although the proportion of V beta 5+ CD8+ T cells and V beta 6+ CD4+ T cells were increased in the B6 anti-DQw6-B6 MLR T cell line, there was no significant difference in the proportion of peripheral T cells expressing each V alpha or V beta region between B6 and DQw6-B6. Both CD4+ and CD8+ long term-cultured T lymphocyte cell lines were generated from lymph node cells of B6 stimulated in vitro by irradiated spleen cells from DQw6-B6. The CD4+ T cell line proliferated in response to spleen cells of DQw6-B6 or L cell transfectant expressing HLA-DQw6 molecules and these responses were completely inhibited by either anti-DQ or anti-CD4 monoclonal antibodies (mAbs) but not by anti I-Ab mAbs. The CD8+ T cell line lysed splenic cells activated by lipopolysaccharide (LPS) from DQw6-B6 spleen cells but not from B6. The CD8+ T cell line also exhibited a cytotoxicity to splenic LPS blast cells from backcross progenies between (DQw6-B6 x DBA1) F1 and DBA1, only when target cells expressed both HLA-DQw6 molecules and H-2b. These observations indicated that recognition of HLA-DQw6 by the CD8+ cytotoxic T cell line was restricted by H-2b. The cytolytic activity of the CD8+ T cell line was inhibited by either anti-CD8 or anti-H-2Db mAbs but not by anti-HLA-DQ nor anti-H-2Kb mAbs. These results show that HLA-DQ transgene products expressed in DQw6-B6 can induce xenogeneic MLR in both CD4+ and CD8+ T cells. The CD4+ T lymphocytes recognize the HLA-DQw6 molecule itself whereas the CD8+ cytotoxic T lymphocytes recognize the HLA-DQw6 gene product in the context of H-2Db.
 ...
PMID:[Immunological function of HLA-DQw6 molecules expressed in DQw6 transgenic C57BL/6 mice]. 202 62

Methylation of the S gamma 1 switch region and C gamma 1 constant region gene from the immunoglobulin heavy chain locus and of the J beta 2 and C beta regions from the T cell receptor beta chain (TcR beta) locus is compared here in murine germ-line cells, nonlymphoid cells and lymphocytes. In germ-line cells and in lymphocytes prior to recombination all four regions show strong methylation, i.e. most Msp I sites are methylated. After activation of lymphocytes, demethylation is observed for those regions which are activated for recombination, at specific sites 5' of S gamma 1 in B cells activated with bacterial lipopolysaccharide and interleukin 4, and for J beta 2 in thymocytes. In nonlymphoid cells, where these regions cannot be used for recombination, considerable demethylation is observed for all four regions analyzed as compared to lymphocytes. The result implies an important role for methylation of recombinatorial regions. Methylation may be involved in protecting them from uninduced recombination, thus allowing regulated expression of distinct genes in lymphocyte ontogeny.
 ...
PMID:Protective methylation of immunoglobulin and T cell receptor (TcR) gene loci prior to induction of class switch and TcR recombination. 212 53

Blast cell populations from 32 patients with acute non-lymphoblastic leukaemia of various morphological types have been examined for their ability to stimulate allogeneic T lymphocytes from normal donors in one-way mixed leucocyte culture (MLC). At the same time, these leukaemic cell populations were examined for the amounts of major histocompatibility complex Class I and Class II antigens they expressed, and their ability to release interleukin 1 (IL1) in culture both with and without stimulation by lipopolysaccharide. The abilities of the leukaemic cell populations to stimulate in MLC, and to produce IL1, were found to be associated with the expression of morphological characteristics of monocytic differentiation, and correlated significantly. In contrast, no correlation was observed between the extent of Class I or Class II expression and MLC stimulatory ability. Many myeloblast populations of immature phenotype were unable to stimulate allogeneic T cells despite their strong expression of these antigens. This lack of stimulatory ability was not overcome by the addition of exogenous IL1. We therefore conclude that the correlation between the production of IL1 and MLC stimulatory ability does not necessarily imply a cause/effect relationship, and that the interaction between allo-antigen and the T cell receptor together with a supply of lymphokine 'co-stimulator' is not sufficient to activate resting T lymphocytes. The failure of some Class I and II antigen positive leukaemic blasts to stimulate in MLC even in the presence of exogenous IL1 may be due to the lack of other differentiation-associated cell surface molecules necessary for stable cell-cell interaction.
 ...
PMID:Requirements for the stimulation of allogeneic T lymphocytes by acute non-lymphoblastic leukaemia cells. 296 Apr 48

We have analyzed the role of cognate interaction with helper T cells (Th) in support of resting B cell differentiation to plaque formation. Co-culture of histoincompatible resting B cells and resting Th cells resulted in the induction of plaque-forming cells when dimeric but not monomeric fragments of anti-T cell receptor (TcR) antibody were added to culture. The efficiency of B cell activation was comparable to that supported by lipopolysaccharide and lectin-mediated Th-B cell conjugate formation. Further, if resting Th cells were preactivated with antigen and histocompatible antigen-presenting cells, the requirement for addition of anti-TcR to mixtures of histoincompatible Th and B cells was obviated. These results demonstrate that TcR-mediated Th recognition of major histoincompatibility complex class II/antigen composites on the resting B cell membrane does not provide obligate signals for B cell differentiation to plaque formation. We are left with two possibilities. Either the entire process of Th cell-dependent induction of resting B cell differentiation is mediated by soluble lymphokines or if Th-B cell contact is mandatory, it is mediated through nonpolymorphic cell surface determinants.
 ...
PMID:T helper cell-dependent induction of resting B cell differentiation need not require cognate cell interactions. 296 44

Antibodies directed against the human T cell receptor or the closely associated CD3 molecule stimulate polyclonal T cell proliferation via mechanisms that mimic a primary immune response. We have investigated the requirement for IL-1 production in anti-CD3 (OKT3)-mediated mitogenesis using a Hodgkin's disease cell line (L428) as the accessory cell. L428 cells did not produce detectable IL-1 following stimulation with lipopolysaccharide or phorbol ester (PMA), nor did they transcribe detectable levels of mRNA for IL-1 alpha or beta after such treatment. Despite their inability to produce IL-1, as few as 1 X 10(4) L428 cells reconstituted the proliferative response of accessory cell-depleted T cells to anti-CD3. Although larger numbers of non-rosette-forming (E-) cells were required for maximal responsiveness to anti-CD3, the maximal degree of proliferation was higher with E- cells than with L428 cells. L428-mediated T cell proliferation did not result from residual accessory cells in the responding population or an allogeneic effect since L428 cells were also capable of providing accessory cell activity for the anti-CD3-dependent generation of IL-2 by the Jurkat T cell line. Although the mechanism by which L428 cells provide accessory functions remains incompletely characterized, the ability of anti-HLA-DR F(ab')2 fragments to completely abrogate L428 and monocyte-mediated anti-CD3 mitogenesis, despite the addition of exogenous IL-1, provides evidence for the participation HLA-DR molecules in this response. These data indicate that anti-CD3-induced proliferation of unprimed human T lymphocytes can occur independently of IL-1 production by accessory cells and may involve the participation of HLA-DR molecules.
 ...
PMID:Interleukin-1-independent activation of human T lymphocytes stimulated by anti-CD3 and a Hodgkin's disease cell line with accessory cell activity. 297 87

The cyclic undecapeptide cyclosporine A (CsA) is a potent immunosuppressive agent that inhibits the initial activation of T lymphocytes. This agent appears to be most effective in blocking the action of mitogens such as concanavalin A and the calcium ionophore A23187, which cause an influx of Ca2+, but not those that may act by alternate mechanisms. These observations suggest that CsA may block a Ca2+-dependent step in T cell activation. We have shown that stimulation of the T3-T cell receptor complex-associated Ca2+ transporter activates the Na+/H+ antiport (Rosoff, P. M., and L. C. Cantley, 1985, J. Biol. Chem., 260: 14053-14059). The tumor-promoting phorbol esters, which are co-mitogenic for T cells, activate the exchanger by a separate pathway which is mediated by protein kinase C. Both the rise in intracellular Ca2+ and intracellular pH may be necessary for the successful triggering of cellular activation. In this report we show that CsA blocks the T3-T cell receptor-stimulated, Ca2+ influx-dependent activation of Na+/H+ exchange, but not the phorbol ester-mediated pathway in a transformed human T cell line. CsA inhibited mitogen-stimulation of interleukin-2 production in a separate cell line. CsA also inhibited vasopressin stimulation of the antiporter in normal rat kidney fibroblasts, but had no effect on serum or 12-O-tetradecanoyl phorbol 13-acetate stimulation. CsA did not affect serum or vasopressin or serum stimulation of normal rat kidney cell proliferation. CsA also had no effect on lipopolysaccharide or phorbol ester stimulation of Na+/H+ exchange activity or induction of differentiation in 70Z/3 pre-B lymphocytes in which these events are initiated by the protein kinase C pathway. These data suggest that mechanisms of activation of Na+/H+ exchange that involve an elevation in cytosolic Ca2+ are blocked by CsA but that C kinase-mediated regulation is unaffected. The importance of the Na+/H+ antiport in the regulation of growth and differentiation of T cells is discussed.
 ...
PMID:Cyclosporine A inhibits Ca2+-dependent stimulation of the Na+/H+ antiport in human T cells. 301 82

Monoclonal antibodies detecting idiotopes on the germ line-encoded anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) antibody B1-8 were injected at various doses into newborn mice and the expression of B1-8 idiotopes was measured in anti-NP responses in later life. Suppression was long lasting, and a 100-fold increase in the dose of anti-idiotope delayed recovery from suppression by 5-6 weeks. Upon injection of a single anti-idiotope, suppression was observed for all B1-8 idiotopes to various degrees. Certain idiotopically defined antibody phenotypes were much more efficiently suppressed, and later recovered from suppression, than others. This specificity pattern was observed at the level of both B and T cells from the manipulated animals, as demonstrated in cell transfer experiments in which such cells were mixed with normal T and B cells. In these experiments, there was evidence for suppression mediated by regulatory T (and possibly also B) cells. Whereas the B cells from the manipulated animals were idiotypically unresponsive in a T cell-dependent adoptive primary response, the frequency of lipopolysaccharide-reactive B cells expressing the target idiotype was only slightly reduced in these animals as compared to control mice. Together with data on the elimination of anti-idiotope antibody from the neonatally injected animals these results are interpreted in the following way: idiotype suppression is induced through the reaction of anti-idiotope with idiotopes expressed on the surface of newly generated B cells, at microgram concentrations of anti-idiotope. When the concentration of anti-idiotope fall below that level, recovery from suppression sets in. Two types of suppression are induced. The first, namely, direct blockade of B cell maturation, is short-lived. The second involves the induction of regulatory cells, perhaps through idiotope-bearing antibody V regions complexed by anti-idiotope. This type of suppression is long-lived and its specificity depends upon the distribution of the target idiotope in the antibody repertoire and/or peculiarities of the T cell receptor repertoire. It impinges on the selection of the B cell repertoire in the animal as expressed in T cell-dependent (and possibly other) responses and is thus hardly seen at the level of lipopolysaccharide-reactive (immature) cells. Idiotype suppression by regulatory cells may be perpetuated by antigen interacting with idiotypic antibodies on the B cell surface and may therefore play a role in establishing tolerance not only for the expressed antibody repertoire, but for self antigens in general.
 ...
PMID:Specificity, duration and mechanism of idiotype suppression induced by neonatal injection of monoclonal anti-idiotope antibodies into mice. 661 Dec 68


1 2 3 4 5 6 7 Next >>