bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resistance to cellular immune response in AKR leukemias
Authors: Schäfer Andreas , Schmidt Wilhelm 
Published: February 2007

AbstractSpontaneous AKR leukemias express murine leukemia virus (MuLV) gag and env gene‐encoded structural proteins on their cell surface. Cytotoxic T lymphocytes (CTL) induced in AKR mice by syngeneic leukemia 369 which expressed high amounts of H‐2 antigens recognized viral gag polyproteins in association with H‐2K antigens as target antigens. H‐2K‐negative leukemias were resistant to lysis by AKR/ Gross MuLV‐specific CTL and did not induce a cellular immune response. However, they became susceptible after stimulation with interferon. H‐2K‐positive leukemias induced CTL which were cytotoxic for 369 cells. However, the majority of H‐2K‐ positive leukemias was not lysed by CTL induced by autologous immunization. These leukemias were also resistant to lysis by anti‐369 CTL, but could restimulate AKR/ Gross‐specific CTL in vitro, and were susceptible to lysis by H‐2Kk‐ restricted CTL against AKR minor histocompatibility antigens. Thus, there could be specific defects of the H‐2Kk antigens of these tumors. However, there were also qualitative and quantitative differences in antigenic determinants of the gag target antigens in these leukemias.
Interferon: a cytotoxic T lymphocyte differentiation signal
Authors: Chen Likuang , Tourvieille Bcatrice , Burns Gordon F. , Bach Fritz H. , Mathieu‐Mahul Danièle , Sasportes Marilyne , Bensussan Armand 
Published: February 2007

AbstractHuman T cell clones which were able to proliferate in response to specific stimuli but could not kill even in the presence of lectins were found to acquire the specific lytic function when interferon alpha or gamma was added on day 1 of the 7‐day restimulation culture. These results demonstrate that interferon may act as a cytotoxic T lymphocyte differentiation signal. This signal can be blocked by the monoclonal antibody LeoA1 which recognizes a 70‐kDa cell surface structure, involved in cytotoxic T lymphocyte differentiation.
Differentiation factors for human specific B cell response
Authors: Vazquez Aimé , Gerard Jean‐Philippe , Delfraissy Jean‐François , Dugas Bernard , Auffredou Marie‐Thérèse , Crevon Marie‐Claude , Fradelizi Didier , Galanaud Pierre 
Published: February 2007

AbstractNonspecific T cell factors produced by lectin‐activated human peripheral blood lymphocytes (PBL) were used to restore the T‐dependent B cell response to trinitro‐phenyl‐polyacrylamide (TNP‐PAA). Preincubation experiments with the particulate antigen TNP‐PAA and/or a soluble TNP‐protein conjugate show that a first specific signal provided by the antigen and nonspecific lymphokines sequentially acts on B cells. By gel filtration the T cell‐replacing factor (TRF) activity is present in the 30–15‐kDa fraction of T cell supernatants and is associated to interleukin 2 (IL 2). However, absorption of IL 2 does not abolish the TRF activity. Moreover, chromatofocusing of this 30–15‐kDa material allows the obtaining of an IL2‐free fraction containing a differentiation factor (with an isoelectric point of 5.7 ± 0.2). The ability of this fraction to restore the anti‐TNP response is manifest in the presence of a 50‐kDa B cell growth factor. This latter, prepared by a combination of absorption on concanavalin A‐Sepharose and gel filtration, was IL2 free and unable to support the anti‐TNP response. We thus directly demonstrate that in the absence of IL2 three separate signals (the antigen, T cell‐derived growth and differentiation factors) are involved in human‐specific B cell response.
Unrestricted recognition of class I neodeterminants generated by exon shuffling
Authors: Horstmann Ulrike , Arnold Bernd , Hämmerling Günter J. 
Published: February 2007

AbstractWe and others have previously reported that homologous exchange of ä1 or α2domains between different alleles led to loss of most determinants recognized by cytotoxic T lymphocytes (CTL) raised against the parental H‐2 class I antigens. Here we demonstrate that exchange of α1 or α2 domains between the Kk and Kd allele results in the formation of neodeterminants against which allospecific CTL can be generated in responder mice of various related and unrelated H‐2 haplotypes. In fact, only CTL against the neodeterminants on the hybrid molecules were found and none against the parental Kk and Kd determinants. In addition our data show that recognition of the neodeterminants is H‐2 unrestricted. These findings suggest that in the hybrid molecules the basic structure of a major histocompatibility complex molecule has been preserved although most parental allodeterminants on the α1 and α2 domains have been modified.
Autoreactive or self restricted?
Authors: Julius Michael H. , Heusser Christoph H. 
Published: February 2007

AbstractPutative major histocompatibility complex (MHC) class II‐specific T cell clones were isolated from nominal antigen‐primed T cell populations propagated in vitro under antigen selection. However, unlike the proliferative responses of nominal antigen‐specific, MHC class II‐restricted T cell clones derived from the same population, the former's MHC‐specific proliferative responses required that the culture medium be supplemented with serum. The role of xenogeneic antigens in the generation of this category of “autoreactive” T cells is discussed.
The bulk of endogenously produced IgG2a is eliminated from the serum of adult C57BL/6 mice with a half‐life of 6–8 days
Authors: Vieira Paulo , Rajewsky Klaus 
Published: February 2007

AbstractThe concentration of IgG2a in the serum of C57BL/6 mice suppressed for the production of IgG2a was measured over a period of 3 months after suppression. The elimination of a minimum of 96% of the endogenous IgG2a molecules from the serum follows an exponential decay with a half‐life of 6–8 days. A monoclonal IgG2a antibody injected into suppressed or normal mice is eliminated from the serum in the same fashion. We conclude that there are few, if any, “long‐lived” IgG2a molecules present in the serum of C57BL/6 mice under physiological conditions.
An investigation of T cell receptor gene rearrangement and expression in organ cultures of normal embryonic thymus and Thy‐1+ cells of nude mice
Authors: Owen Michael J. , Jenkinson Eric J. , Williams Gwyn T. , Kingston Rosetta , Owen John J. T. 
Published: February 2007

AbstractWe have shown that beginning with 14‐day mouse embryo thymus, rearrangements of T cell receptor β‐chain genes and transcripts of α and β chains culminating in the generation of T cell receptor‐bearings cells can be obtained in organ cultures. We have failed to detect rearrangement β chain genes, and β chain transcripts or membrane receptors in concanavalin A‐activated nude spleen cells, although we cannot exclude the possibility that a minor subpopulation of nude Thy‐1+ cells may express T cell receptors. Our results suggest that the thymus is both necessary and sufficient for generation of T cell receptor‐bearing cell and that organ culture provides a system for further investigation of the mechanisms involved.
Antibodies reactive with the B1 molecule inhibit cell cycle progression but not activation of human B lymphocytes
Authors: Tedder Thomas F. , Forsgren Arne , Boyd Andrew W. , Nadler Lee M. , Schlossman Stuart F. 
Published: February 2007

AbstractThe B1 cell surface molecule (CD20) is a 35‐kDa phosphoprotein expressed by B lineage cells during most stages of differentiation. Some monoclonal antibodies reactive with B1 induce activation while others, anti‐B1a, inhibit B lymphocyte function. To further determine the requirement of B1 molecule function in proliferation and differentiation the effects of anti‐B1a antibody binding on early cellular activation events were examined. Immunoglobulin secretion of lymphocyte cultures stimulated with pokeweed mitogen was maximally inhibited if the antibody (1‐10μg/ml) was added during the first 24 h of culture. However, even high antibody concentrations were unable to inhibit increases in free intracellular Ca2+ concentrations immediately following cross‐linkage of cell surface immunoglobulin, or inhibit cell enlargement and the expression of transferrin and interleukin 2 receptors. Antibody binding to B1 inhibited RNA synthesis (37‐80%) and progression through cell cycle following activation. In contrast, proliferation induced by phorbol myristate acetate was not inhibited by antibody binding to the B1 molecule. The findings that the earliest activation events and phorbol myristate acetate‐induced proliferation were not inhibited by antibody binding to B1 suggest that inhibition is due to the blocking of a step of the activation process required for cell cycle progression and differentiation, rather than blocking initial signal transduction across the membrane or providing a negative or suppressive signal.
Characterization of the role for calcium influx in mitogen‐induced triggering of human T cells. Identification of calcium‐dependent and calcium‐independent signals
Authors: Gelfand Erwin W. , Cheung Roy K. , Grinstein Sergio , Mills Gordon B. 
Published: February 2007

AbstractEntry of Ca2+ into the cell is recognized as an important activation signal for mitogeninduced lymphocyte proliferation. Changes in free cytosolic Ca2+ ([Ca2+]i) can now be measured directly using the fluorescent reagent quin‐2. To analyze the role of [Ca2+]i in human T cell activation, we have determined the effect of the calcium channel blocker, nifedipine, on phytohemagglutinin (PHA)‐induced lymphocyte proliferation. At a concentration of 50 μM, nifedipine is nontoxic, and prevents PHA‐induced proliferation. In parallel the drug prevents the lectin‐induced increase in concentration of [Ca2+]i and interleukin 2 (IL2) secretion; IL2 receptor expression is unaffected. In the presence of exogenous IL2, cell proliferation proceeds normally. Treatment of the cells with the tumor promoter 12‐O‐tetradecanoylphorbol 13‐acetate prevents the inhibitory effect of nifedipine on cell proliferation. Since TPA is itself nonmitogenic and does not affect levels of cytosolic Ca2+, these data and the data on IL2 receptor expression indicate that PHA can generate an activation signal(s) which is [Ca2+]i independent.
The roles of interleukin 2 and interferon‐γ in human B cell activation, growth and differentiation
Authors: Jelinek Diane F. , Splawski Judy B. , Lipsky Peter E. 
Published: February 2007

AbstractThe roles of interleukin 2 (IL 2) and interferon‐γ (IFN‐γ) in human peripheral blood B cell activation, growth and differentiation were examined. Highly purified B cells stimulated with Cowan I Staphylococcus aureus (SA) proliferated minimally and generated no immunoglobulin‐secreting cells (ISC) without the addition of T cell supernatants (T sup) produced by mitogen‐activated T cells. Recombinant IL 2 (rIL 2) alone was able to promote maximum proliferation and generation of ISC in cultures of highly purified SA‐stimulated B cells when present from the initiation of the incubation. IFN‐γ, by contrast, could not support either response alone. When a twostep culture system was employed to determine the effect(s) of T cell influences during both initial activation and in propagating the response following activation, it was found that B cells activated by SA alone subsequently responded maximally to T sup but only minimally to IL 2 and not at all to IFN‐γ. However, the presence of T sup, rIL 2, or rIFN‐γ during initial activation with SA was found to facilitate greatly the subsequent capacity of the activated B cells to proliferate and differentiate in response to either T sup or IL 2. These data suggest two distinct pathways of human B cell responsiveness. Activities in T sup other than IL 2 or IFN‐γ can support the growth and differentiation of B cells initially activated with SA alone, whereas rIL 2 is capable of promoting these responses maximally only when B cells have been initially activated by SA in the presence of T cell lymphokines, such as IL 2 or IFN‐γ. The results emphasize the role of specific T cell factors in determining the outcome of humoral immune responses.
Lysis of bystander target cells after triggering of human cytotoxic T lymphocytes
Authors: Fleischer Bernhard 
Published: February 2007

AbstractHuman cloned cytotoxic T lymphocytes (CTL) specific for class I HLA antigens were used to investigate whether triggering of CTL leads to killing of innocent bystander target cells. After triggering of CTL by their specific target cells, lysis of bystander targets was detected in a 7‐h cytotoxicity assay. Considerable differences were found in the susceptibility of various target cells to this type of lysis. Targets susceptible to this bystander lysis were also susceptible to lysis by CTL triggered by F(ab')2 fragments of an anti‐T3 monoclonal antibody, whereas other targets were resistant to both types of cytotoxicity. Triggering of CTL by oxidized target cells or via a T3‐independent activation pathway led to bystander lysis detectable already after 4 h. Bystander lysis was considerably enhanced under conditions that facilitated a nonspecific cell contact between CTL and bystander target. We conclude that a function besides antigen recognition of the T cell receptor on CTL is to direct killing to the target cell. This directing, however, is incomplete and destruction of innocent bystanders can be detected under appropriate conditions.
Transhybridomas from fusion gene transgenic lymphocytes can be used to produce foreign protein of biological interest
Authors: Babinet Charles , Morello Dominique , Rougeot Catherine , Rouyre Sylvie 
Published: February 2007

AbstractA method is described for achieving the efficient production of proteins of biological interest by the establishment of hybridomas from lymphocytes of transgenic animals carrying a fusion gene having promoter‐regulatory sequences functional in lymphocytes fused to the coding sequences of the protein to be produced. While possible improvements in the method are discussed, it is anticipated that the method will ultimately be applicable to the production of any protein of interest.
Priming immune response to cholera toxin induced by synthetic peptides
Authors: Jacob Chaim O. , Grossfeld Shoshana , Sela Michael , Arnon Ruth 
Published: February 2007

AbstractA systematic study has been conducted of the priming effect in the immunization against cholera toxin (CT). We demonstrate that a priming phenomenon can be achieved by synthetic peptides of the CT B subunit, leading (after a subsequent booster with a subimmunizing dose of the intact toxin) to an efficient anti‐CT neutralizing antibody response. This effect is obtained even upon a single administration of a peptide conjugate and even by peptides that as such are not able to induce CT cross‐reactive antibodies whatsoever. This effect is specific and dose dependent. A macromolecular carrier as well as an adjuvant are essential for the induction of antitoxin response. In this respect, a totally synthetic priming agent, CTP3‐poly (DL‐alanyl)–poly(L‐lysine), was adequate for an effective priming response. The specificity of the antibodies formed after the booster was mainly towards the whole CT molecule and only a small fraction of them were specific towards the peptide used for priming. The ability of synthetic peptides to prime the immune system towards a secondary stimulus with whole organism or native protein might be of general practical value, especially in endemic areas where the population is probably constantly exposed to a low level of a particular infectious agent. This exposure, which has no influence on the unprimed immune system, could serve as a booster in the case of individuals primed with an appropriate peptide, leading to a secondary immune response.
Functional characterization of monoclonal auto‐antiidiotype antibodies isolated from the early B cell repertoire of BALB/c mice
Authors: Vakil Meenal , Kearney John F. 
Published: February 2007

AbstractA large number of hybridomas were constructed by fusion of B cells from perinatal liver and spleen. Many of these showed multispecificity, high interconnectivity and anti‐idiotype (Id) activity. Several of these were subjected to a detailed analysis to evaluate their influence on the developing immune system.A hybridoma BD2 (μ,χ), derived from 2‐day‐old liver, was shown to have anti‐T15 and anti‐J558 activity by inhibition enzyme‐linked immunosorbent assay and by in vivo administration. BD2 reduced primary T15 and J558 Id in adult BALB/c by 50%. In contrast, timed administration of this antibody during neonatal periods resulted in enhancement of responses to phosphorylcholine (PC) and a(l ‐>3)‐linked dextran (Dex) when these mice were challenged as adults. Another hybridoma DB3 (μ,χ), derived from a lipopolysaccharide‐stimulated fetal liver, reacts with GB4–10 (anti‐ T15) and not with PC. It also reacts with BD2. It is thus anti‐anti‐Id with respect to T15 and J558. Early administration of this antibody also led to an enhancement of anti‐PC and anti‐Dex responses, apparently via expansion of a set of intermediate anti‐Id BD2‐like B cells. In adult mice it suppressed responses to both antigens. A third hybridoma FC4 (μ,χ), derived from 3‐day‐old spleen, reacts with GB4–10 as well as EB3–7 (anti‐J558). Introduction of this antibody into neonatal mice enhanced anti‐ Dex responses while in adults it caused suppression of T15 Id. The results presented here suggest a possible role for neonatal anti‐Id B cells in the primary activation of antigen‐reactive B cells by Id selection.
T cell involvement in the decrease of antigen‐responsive B cells in aged mice
Authors: Zharhary Dorith 
Published: February 2007

AbstractThe role of T cells in the reduced frequency of splenic B cells specific for several antigens in aged mice was studied by assessing B cell responsiveness in (a) aged nude mice and (b) irradiated young mice repopulated with splenic B cells or with Ig− bone marrow cells from young mice and T cells from aged vs. young mice. Using the fragment culture technique to assess B cells specific for 2,4‐dinitrophenyl (DNP) and for (4‐hydroxy‐3,5‐dinitrophenyl) acetyl, we found that the frequency of responsive splenic B cells in aged B ALB/c nude mice was very similar to that of young nude mice. In addition, we found that in chimeric mice constructed with either bone marrow or splenic B cells from young mice and T cells from aged mice the frequency of DNP‐ specific splenic B cells was significantly lower than that in control chimeras constructed with T cells from young mice. These results indicate that T cells from aged mice can down regulate B cell responsiveness and that a mature, naive B cell may be its possible target. The results of both experimental approaches are consistent with a role for T cells in the regulation of responsive B cells in aging.
Isolation and characterization of maerophage‐derived C1q and its similarities to serum C1q
Authors: Rabs Ulrich , Martin Harry , Hitschold Thomas , Golan Mario D. , Heinz Hans‐Peter , Loos Michael 
Published: February 2007

AbstractRecently, we have shown that the collagen‐like, Fc‐recognizing subcomponent C1q of the first complement component is synthesized by human, guinea pig and mouse peritoneal macrophages. To test whether macrophages may contribute to the serum pool of C1q, C1q was purified from guinea pig serum and from guinea pig peritoneal macrophage supernatants and compared for similarities. Both molecules had a similar sedimentation rate (macrophage C1q: 11.3S, serum C1q: 11.2S) and showed on sodium dodecyl sulfate‐polyacrylamide gel electrophoresis under reducing conditions three identical bands with molecular weights of Mr 29 000, Mr 27 000 and Mr 23 000 for the A, B and C chains, respectively. Both C1q molecules migrated by immunoelec‐ trophoresis in the gamma region and, in Ouchterlony analysis, showed complete antigenic identity with rabbit anti‐serum C1q. These experiments demonstrate the antigenic and protein chemical similarities between serum C1q and C1q secreted by macrophages supporting the idea that macrophages have to be considered as one potential source of serum C1q. Furthermore, macrophage‐derived C1q may be of importance in the local microenvironment at an inflammatory site involving macrophages.
Immune serum from mice contact‐sensitized with picryl chloride contains an antigen‐specific T cell factor that transfers immediate cutaneous reactivity
Authors: Van Loveren Henk , Ratziaff Robert E. , Kato Kazuyuki , Meade Robin , Ferguson Thomas A. , Michael Iverson G. , Janeway Charles A. , Askenase Philip W. 
Published: February 2007

AbstractThis report describes an activity in serum from mice that were contact‐sensitized with picryl chloride (PCl) 1 to 4 days earlier. Immune serum, when given i.v., transfers the ability to elicit an immediate hypersensitivity‐like ear swelling reaction in naive recipients following local challenge with PCl. This serum activity is due to an antigen‐ binding T cell factor that shares some properties with IgE antibody. The activity is antigen specific, and due to an antigen‐binding moiety that is heat labile (56°C, 4 h). However, unlike IgE antibody the serum activity is resistant to reduction and alkylation, and is retained by columns of Sepharose beads coupled with polyclonal or monoclonal antibodies that react with antigen‐specific T cell factors from other systems. These columns did not retain IgE antibody activity in our experiments. Importantly, the serum activity was not retained by columns linked with antibodies directed to mouse immunoglobulins, which do retain IgE activity.We conclude from these data that the activity in PCl immune serum is not caused by IgE antibody, and is due to the presence of the previously described antigen‐specific T cell factor (PCl‐factor), that can activate serotonin‐containing cells, such as mast cells, to release the vasoactive amine serotonin. PCl‐factor transfers the ability to elicit an immediate hypersensitivity‐like reaction that is an early component of delayed‐type hypersensitivity. The presence of this T cell factor in the serum of actively sensitized mice provides a means to sensitize tissues throughout the body for this required, initial, serotonin‐dependent component of delayed‐type hypersensitivity reactions.
Induction of human interleukin 1 by bacterial and synthetic lipid A
Authors: Loppnow Harald , Brade Lore , Brade Helmut , Rietschel Ernst Theodor , Kusumoto Shoichi , Shiba Tetsuo , Flad Hans‐Dieter 
Published: February 2007

AbstractLipopolysaccharides (LPS) are well known inducers of interleukin 1 (IL1). Here we show that synthetic heptaacyl Salmonella minnesota (compound 516) and synthetic E. coli type (compound 506) lipid A, as well as monodephospho part structures thereof, are able to induce IL1 production in human mononuclear cells. The 4′‐monodephospho part structure (compound 505) was found to be the most active IL1 inducer as compared to compound 506 and the 1‐monodephospho part structure (compound 504). Synthetic lipid A precursor Ia, lacking nonhydroxylated fatty acids (compound 406), and its 1‐ or 4′‐monodephospho part structures (compounds 404 and 405) did not induce IL 1 production. IL2 is not produced during stimulation with the synthetic compounds. IL1 activity was partially heat labile and could be inhibited by a rabbit antiserum against human leukocytic pyrogen. These results show that the lipid A component of LPS is active in inducing IL 1 and that the presence of 3‐acyloxyacyl residues is necessary for IL1 induction.