bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinant interleukin 2 differentiates alloantigen‐primed Lyt‐2+ T cells into the activated cytotoxic state
Authors: Yoshimoto Ryota , Kashima Nobukazu , Okada Kyoko , Amikura Keiko , Hamuro Junji 
Published: February 2007

AbstractThe possibility of the generation of secondary cytotoxic T lymphocyte (2oCTL) activity from alloantigen primed T cells by genetically homogeneous recombinant human interleukin 2 (G‐IL2) was analyzed. Not only purified IL2 by cell culture (C‐IL2) but also G‐IL2 induced 2oCTL activity from primed T cells generated in mixed lymphocyte culture. This induction process required RNA and protein synthesis, while DNA synthesis was not relevant. In parallel to the induction of 2oCTL activity, transition of the primed cells from the resting G1a to activated G1b has taken place. 2oCTL activity was induced from nylon column‐purified primed T cells in the absence of accessory cells and also in the absence of Lyt‐1+ T cells. Interferon‐y (IFN‐γ) induction was detected during the course of activation of alloantigen‐primed T cells into the cytotoxic state. When IL2 was absorbed, IFNγ in the culture supernatant did not induce 2oCTL activity. These results suggest that the IL2 molecule possessing T cell growth factor properties shares the nature of differentiation factor in terms of the activation of alloantigen‐primed T cells into cytotoxic state. The role of IFN‐γ produced in situ for this activation process awaits further investigation.
Enumeration of lymphocyte‐target cell conjugates by cytofluorometry
Authors: Berke Gideon 
Published: February 2007

AbstractUsing fluorescein‐labeled effector lymphocytes and tetramethyl rhodamine‐labeled target cells a cytofluorometric method is described for the detection and quantification of lymphocyte‐target cell cluster (conjugate) formation. Conjugation levels mea‐ sured by cytofluorography correspond well with those scored microscopically. The method has so far been used successfully to monitor conjugate formation by specifically sensitized cytotoxic T lymphocytes (CTL). In preliminary experiments it has been applied to nonspecific, lectin concanavalin A‐dependent conjugate formation by CTL, as well as to conjugates formed by hybridoma CTL. The procedure has potential application in other cell‐cell interactions, relevant to immunology as well as to cell biology.
Antigen processing by macrophages: definition of the ligand recognized by T‐inducer cells
Authors: Puri Joseph , Abromson‐Leeman Sara , Cantor Harvey 
Published: February 2007

AbstractAn interaction between antigen and macrophage‐like cells which display I region gene products [antigen‐presenting cells (APC)] is necessary for activation of inducer T cell clones. The specificity of inducer cell activation has been found to be major histocom‐ patibility complex (MHC)‐restricted and antigen specific. This is thought to reflect formation of a ligand consisting of MHC class II gene products associated in some way with foreign protein.A panel of inducer T cell clones with different activation specificities and homogene‐ ous lines of APC expressing different MHC haplotypes was used to define this ligand. We isolated a product formed after interaction between antigen and APC expressing defined MHC products. This ligand binds only to the T cell clones that are specifically activated by the same antigen and APC as judged by tritiated thymidine incorpora‐ tion. The ligand is composed of two moieties: I‐A determinants and the foreign protein (“antigen”). Coelution and sequential precipitation studies of the two moieties indicate that the nominal antigen and MHC product are tightly linked. The implications of these findings are discussed.
Activation of Lyt‐2+ T cells by antibodies towards brain‐associated antigens. I. Accessory cell requirement and role of Fc receptors in the induction of reactivity to interleukin 2
Authors: Gullberg Martin , Carlsson Sven R. , Larsson Eva‐Lotta 
Published: February 2007

AbstractThe present report describes a system where essentially all Lyt‐2+ T cells are selectively activated by rabbit anti‐mouse brain antibodies (RaMB) to interleukin 2 (IL 2) reactivity. High efficiency of RaMB‐mediated induction was obtained by a 5 h incubation with antibodies at high cell density of Sephadex G‐10‐nonadherent spleen cells. No in situ production of IL 2 by RaMB‐treated cells was detected, and proliferalive responses were entirely dependent on exogeneous IL2. RaMB‐induced IL2 reactivity was found to require accessory cells which are Fc receptor positive, and clearly distinct from those required to induce T cell proliferation in mixed lymphocyte cultures. We conclude that Lyt‐2+ T cells are triggered to IL2 reactivity by Fc receptor ‐ mediated presentation of RaMB antibodies. The mechanism of induction by RaMB antibodies is discussed. This work was supported by the Swedish Medical Research Council, Stiftelsen Jubileumskliniken (Lions project 254/82) Umea, Sweden, and a grant from the Ministry of Research and Technology, France.
Signal requirements for the in vitro differentiation of cytotoxic T lymphocytes (CTL): distinct soluble mediators promote preactivation of CTL‐precursors, clonal growth and differentiation into cytotoxic effector cells
Authors: Hardt Conny , Diamantstein Tibor , Wagner Hermann 
Published: February 2007

AbstractWe describe here that the requirement of accessory cells for the polyclonal activation of high‐density (resting) murine T lymphocytes can be bypassed by soluble mediators present in culture supernatants of concanavalin A (Con A)‐activated murine spleen cells. Induction of responsiveness is confined to Lyt‐2+ T cells; GK 1.5+ T helper cells require signals provided by accessory cells. Using this system the lymphokine signal requirements for the polyclonal activation of Lyt‐2+ cytotoxic T lymphocyte (CTL) precursors could be defined. We show that Con A fails to trigger in Lyt‐2+ responder T cells the expression of interleukin 2 (IL 2) receptors and assume that this explains why recombinant (rec) DNA‐derived IL2 fails to induce proliferative responses. Complementation of rec IL2 with an IL2 receptor‐inducing factor (RIF) induces proliferative responses. RIF alone triggers IL2 receptor expression in 10–12% of Lyt‐2+ T cells exposed to Con A. This lymphokine appears to be distinct from colony‐stimulating factor 1, IFN‐γ and IL1.Resting Lyt‐2+ T cells cultured in limiting numbers in the presence of Con A, RIF plus rec IL2 do proliferate, yet exhibit no cytolytic activity. Differentiation into CTL can be brought about by addition of cytotoxic T cell differentiation factor (CTDF). We conclude that the polyclonal activation pathway of CTL from resting CTL precursors can be subdivided into three stages: preactivation, clonal growth and CTL differentiation. Each of these stages appears to be controlled by a distinct lymphokine, RIF, IL2 and CTDF, respectively.
Helper T cell requirements for T15 idiotype expression on phosphorylcholine‐specific antibodies
Authors: Hathcock Karen S. , Kenny James J. , Hodes Richard J. 
Published: February 2007

AbstractThe requirement for idiotype‐specific T Cells was investigated in the T15 idiotype‐ dominant T cell‐dependent response of unprimed BALB/c and (BALB/c × C57BL/6)F1 B cells to phosphorylcholine (PC). It was first demonstrated that cloned keyhole limpet hemocyanin (KLH)‐specific, major histocompatibility complex (MHC)‐restricted T helper (Th) cells as well as heterogeneous KLH‐primed Th populations were capable of generating PC‐specific antibody responses in T‐depleted unprimed B cell populations cultured in the presence of PC‐KLH. The PC‐binding antibody responses generated under these conditions were indistinguishable when assayed for carrier‐hapten linkage requirements, immunoglobulin isotype (predominantly IgM) or PC affinity. Further, it was observed that the PC‐binding antibodies which were generated in the presence of these two T cell populations expressed equivalently high levels of T15 idiotype. Assaying antibody and idiotype by either enzyme‐linked immunosorbent assay or plaque‐forming cell assay yielded similar results. Since monoclonal MHC‐restricted, KLH‐specific Th cells presumably lack any additional T cell populations, these results argue against an absolute requirement for anti‐idiotypic Th cells in the generation of T15‐dominant antibody responses.
Secretion of IgG1 induction factor by T cell clones and hybridomas
Authors: Sideras Paschalis , Bergstedt‐Lindqvist Susanne , MacDonald H. Robson , Severinson Eva 
Published: February 2007

AbstractIgG1 induction factor elevates the IgGl response induced by lipopolysaccharide and suppresses the lipopolysaccharide‐induced IgG3 and IgGZb responses in cultures of mouse spleen cells. We have developed new T cell lines secreting this factor by cloning mixed lymphocyte culture populations. Using supernatants of one of these T cell lines it was found that the assay is quantitative, reproducible and accurate, both when induction of IgGl as well as reduction of IgG3 and IgG2b were measured. Using this analysis, different conditions to induce maximal production of the factor were tested. The cell line was thereafter used as fusion partner with a T cell lymphoma. The hybrids were selected in the presence of T cell growth factor and all of them secreted IgGl induction factor.
HLA class II restriction governing cell cooperation between antigen‐specific helper T lymphocytes, B lymphocytes and monocytes for in vitro antibody production to influenza virus
Authors: Fischer Alain , Sterkers Ghislaine , Charron Dominique , Durandy Anne 
Published: February 2007

AbstractTo study HLA class II compatibility requirement for in vitro antibody production to influenza virus, semipurified T lymphocytes, B lymphocytes and monocytes from HLA‐typed responder donors were used. The presence of the three subpopulations was required for antibody production while a mixture of only two of those was ineffective. When using fresh T lymphocytes which exert an allogeneic suppressive effect and may also exhibit allogeneic helper activity, it was not possible to conclude an HLA class II‐linked restriction of T‐B cell cooperation although there was a suggestion of it. However, a grown H3 hemagglutinin‐specific T cell line (L2), previously shown to be restricted by HLA‐DR molecule (DR1) for interaction with antigen‐presenting cells and devoid of allogeneic reactivity, exerts an HLA class II‐restricted helper activity. This was demonstrated by various combinations of HLA‐DR semi‐compatible or incompatible B lymphocytes and/or monocytes with L2 T cells.The restriction element was identified as an HLA‐DR determined since HLA‐DC‐compatible, HLA‐DR‐incompatible B lymphocytes were not helped by L2 T cells. In addition, monoclonal anti‐HLA‐DR but not anti‐HLA‐DC antibodies directed to the relevant specificity did inhibit the antigen‐specific helper activity.We present evidence that not only T monocyte but also T‐B and/or T‐B‐monocyte interactions are HLA class II restricted.
Stromal cell types in the developing thymus of the normal and nude mouse embryo
Authors: van Vliet Els , Jenkinson Eric J. , Ton Rosetta Kings , Owen John J. T. , van Ewrjk Willem 
Published: February 2007

AbstractThe anatomical distribution of various nonlymphoid cell types in the embryonic mouse thymus in vivo and in vitro, as well as in the thymic rudiment of the nude mouse embryo, has been studied. For this purpose a panel of monoclonal antibodies, ER‐TR3, 4, 5, 6 and 7, directed to various types of stromal cells of the mouse thymus, was used in combination with immunoperoxidase labeling on frozen sections. It was shown that as early as day 13 in thymic ontogeny distinction of TR4+ cortical epithelial cells and TR5+ medullary epithelial cells is possible. Thus, as far as stromal components are concerned, the thymus at day 13 in ontogeny is already subdivided into cortex and medulla. At day 13, Ia (TR3) was expressed in a focal pattern in the medulla subsequently appearing throughout both cortex and medulla by day 16. The thymic rudiment of the nude mouse embryo differs markedly from the normal embryonic thymus in its lack of demonstrable Ia antigen. Furthermore, TR4 and TR5 were only expressed on occasional epithelial cells lining the cysts of the nude thymus in a mutually exclusive fashion. The majority of stromal cells of the nude thymus, however, is negative for all ER‐TR antibodies tested.In addition, we have shown that in organ cultures the organization of the stroma of thymic lobes remains intact, at least for a period of 11 days. Embryonic thymi cultured in the presence of deoxyguanosine, which causes depletion of lymphoid cells, also contain cortical and medullary areas as identified by the presence of TR3,4+ and TR5+ stromal cells. This indicates that the lack of organization in the nude thymus is not simply due to the absence of lymphoid cells.
The selective localization of B lymphocytes in the spleen and the role of complement receptors
Authors: Kraal Georg , van Hoogstraten Ingrid , Klerx Jac P. A. M. , van Dijk Hans 
Published: February 2007

AbstractThe role of complement receptors on the localization of T and B cells in the spleen of mice was studied using short‐term homing experiments in cobra venom factor (CoF)‐ treated animals. The localization ratio of B and T cells in the spleen of CoF‐treated mice decreased significantly compared to control recipients. No changes could be found in the relative distribution of resident T and B cells in the spleen or other lymphoid organs of CoF‐treated animals and when their spleen or lymph node cells were transferred, the localization pattern was normal. When cells were incubated in serum prior to transfer a disturbed localization ratio in the spleen of untreated recipients was observed. This was due to a blockade of complement receptors as determined by the inability of the incubated cells to form EAC rosettes. No blockade of EAC rosettes and no changes in localization ratios upon transfer could be observed when the cells were incubated in functionally C3‐depleted serum. The results suggest a role for the complement‐receptor on B cells in the initial localization in the spleen, whereas no influence upon the selective localization in high endothelial venules‐ bearing organs was found.
Involvement of T3 and T8 molecules in human T cell receptor function. Anti‐T3 or anti‐T8 antibodies do not block the antigen‐dependent activation of a subset of alloreactive cytolytic T cell precursors
Authors: Moretta Alessandro , Pantaleo Giuseppe , Mingari Maria‐Cristina , Moretta Lorenzo 
Published: February 2007

AbstractIn the present study, we have analyzed the effects of anti‐T8 and anti‐T3 monoclonal antibodies (mAb) on the generation of human allospecific cytolytic T lymphocytes (CTL). A sensitive limiting dilution microculture system, in which graded numbers of responder T cells were added to 105 irradiated allogeneic spleen cells and saturating amounts of exogeneous interleukin 2, has been employed to provide minimal estimates of the frequencies of alloreactive CTL precursors (CTL‐P) present in T lymphocyte populations freshly isolated from peripheral blood. Addition of anti‐T8 or anti‐T3 mAb at the onset of micro mixed lymphocyte culture containing peripheral blood T lymphocytes as responding cells caused a 65–80% reduction in the frequency of specific CTL‐P which proliferate under these conditions. Moreover, in most instances (> 80%) the cytolytic activity of those CTL‐P which underwent clonal expansion in the presence of either anti‐T8 or anti‐T3 mAb was found to be resistant to inhibition by the corresponding mAb added during the cytolytic assay. In addition, a great degree of overlap existed between microcultures resistant to anti‐T3 and those resistant to anti‐T8 mAb. In contrast, neither antibody had any inhibitory effect when added later to the cultures, presumably because at this stage CTL‐P had been already triggered by alloantigens. Taken together our data indicate that the heterogeneity in the susceptibility to inhibition by anti‐T3 or anti‐TS mAb, previously observed at the level of CTL clones, is predetermined already at the level of peripheral blood CTL‐P.
Involvement of T11 molecules in antigen receptormediated T lymphocyte functions: effect of anti‐T11 monoclonal antibody on functional capabilities of alloreactive T cell clones
Authors: Moretta Alessandro , Pantaleo Guiseppe , Lopez‐Botet Miguel , Mingari Maria‐Cristina , Carrel Stephane , Moretta Lorenzo 
Published: February 2007

AbstractAs shown by previous studies, the sheep erythrocyte‐binding T11 molecule is involved in T cell activation, as well as in mechanisms of specific allogeneic target cell lysis. In this study, we utilized two anti‐T11 monoclonal antibodies (mAb) that inhibited the specific cytolytic activity of mixed lymphocyte culture (MLC)‐activated T cells to analyze, at the clonal level, the involvement of T11 molecules in (a) antigen‐specific vs. nonspecific mechanisms of target cell lysis, and (b) antigen‐driven T cell proliferation and interleukin 2 (IL2) production vs. IL2‐induced cell proliferation. In contrast to anti‐T3 or anti‐T8 mAb, antibodies to T11 molecules inhibited the cytolytic activity of MLC‐derived allospecific clones in a uniform manner. In addition, anti‐T11 antibodies inhibited the specific activity of cytotoxic T lymphocyte clones resistant to anti‐T3 antibodies, even after antibody‐induced modulation of T3 molecules (while anti‐T3 mAb had no effect). Similarly, anti‐T11 antibodies inhibited the alloantigen‐induced proliferation and IL2 release of alloreactive clones independent of their T4+ or T8+ phenotype. The inhibitory activity of anti‐T11 antibodies appears to be confined to antigen‐specific T cell functions since neither natural killer‐like activity of cytotoxic T lymphocyte clones nor the IL 2‐induced clonal proliferation was affected. Thus, our results indicate that T11 molecules are functionally involved in antigen recognition by T cell regardless of their function and T4/T8 phenotype. The possible mechanisms of anti‐T11 antibody‐mediated inhibition are discussed.
Phytohemagglutinin binds to the 20‐kDa molecule of the T3 complex
Authors: Valentine Mary A. , Tsoukas Constantine D. , Rhodes Gary , Vaughan John H. , Carson Dennis A. 
Published: February 2007

AbstractCurrent findings have suggested that the T3 molecular complex is an essential antigenic signal transducer during T cell activation. Lectins, such as phytohemagglutinin (PHA), activate T cells nonspecifically. Concesivably, lectins may mediate their stimulatory action by affecting the T3 complex. In the present investigation we have studied the involvement of the T3 molecular complex in the PHA‐mediated activation of T cells. We selectively modulated the surface expression of T3 molecules by anti‐T3 antibody and subsequently tested the ability of the modulated cells to respond to PHA. Reduction of T3 expression by 70% resulted in 80% inhibition of the PHA response. This effect was specific for T3 since modulation of other T cell surface molecules (T4, T8) did not affect the PHA‐induced mitogenesis. To determine if PHA could interact directly with the T3 complex, immunoblotting (Western blot) analyses of anti‐T3 immunoprecipitates were performed. A 20‐kDa member of the T3 complex reacted not only with the anti‐T3 antibody, but also with PHA itself. These results provide the first evidence for direct binding of PHA to one of the molecules of the T3 complex. The combined data suggest that a major pathway of PHA‐induced T cell activation involves the T3 complex. Possible activation mechanisms are discussed.
Binding of Coprococcus comes to the Fc portion of IgG. A possible role in the pathogenesis of Crohn's disease?
Authors: van de Merwe Joop P. , Stegeman Jeanette H. 
Published: February 2007

AbstractPrevious studies have shown that the fecal flora of Patients with Crohn's disease (CD) differed from the flora of healthy subjects by a higher number of anaerobic grampositive coccoid rods. Sera from patients with CD agglutinated four strains of coccoid rods (Me44, C18, Me46 and Me47) more frequently and stronger than sera from healthy subjects and patients with other diseases. One of these bacteria, Coprococcus comes strain Me46, was not ingested by neutrophils after coating with specific IgG. In the present study, therefore, the binding of IgG and of Fab and Fc fragments to the four coccoid rods was investigated using immunofluorescence and absorption techniques. Results were compared with those obtained with Staphylococcus aureus strain Cowan I and showed that Me46, like S. aureus, bound (nonspecifically) IgG through its Fc portion whereas strain Me47 bound IgG through the Fab portion. Possible implications of the findings for CD are discussed.
Activation of human T lymphocytes III. Triggering of bystander cytotoxicity in cytotoxic T cell clones by antibodies against the T3 antigen or by a calcium ionophore
Authors: Schrezenmeier Hubert , Kurrle Roland , Wagner Hermann , Fleischer Bernhard 
Published: February 2007

AbstractThe role of T cell differentiation antigens in antigen‐specific and nonspecific cytotoxicity by human cytotoxic T lymphocyte (CTL) clones was investigated. In contrast to other reports, several monoclonal antibodies (mAb) against the T3 antigen only marginally blocked antigen‐specific cytotoxicity at high concentrations but induced cytotoxicity against third party cells at concentrations from 10 to 0.001 μg/ml. Susceptibility to anti‐T3‐induced lysis was variable but was found with all target cells, Incubation of CTL with anti‐T3 mAb even led to self‐destruction of the CTL. The effect was independent of the presence of Fc receptors on the target cell and could be obtained with F(ab')2 fragments of the antibody as well. Only activated but not resting T cells could be induced to lyse by anti‐T3. Furthermore, this type of bystander killing of target cells could also be induced by the Ca2+ ionophore A23187. Antibodies against the T8 differentiation antigen inhibited antigen‐specific, oxidation‐induced and antGT3‐induced cytotoxicity by T8+ CTL clones, whereas triggering by the ionophore A23187 was not inhibited. These results show that undirected killing can be triggered in CTL by activating a transducing molecule directly without involving the antigen receptor. Since this triggering of the lethal hit can still be inhibited by mAb against the T8 molecule, the T8 molecule probably has a regulatory role in a late phase of CTL triggering.
Role of protein synthesis in induction of interferon‐γ by mitogens in human lymphocytes
Authors: Siggens Kenneth W. , Tinsley Jonathan M. , Morris Alan 
Published: February 2007

AbstractThe effect of inhibition of protein synthesis on interferon gamma (IFN‐γ) mRNA induction has been examined in human peripheral blood leukocytes and growing T lymphoblasts. Inhibition of protein synthesis by cycloheximide or puromycin when lymphocytes were stimulated with mitogen alone had little effect on the steady‐state levels of IFN‐γ mRNA induced. Activation of the IFN‐γ gene appears to occur independently of synthesis of protein factors.Synergistic induction of IFN‐γ by mitogen plus the phorbol ester mezerein was at least in part accounted for by increased levels of IFN‐γ mRNA in both fresh lymphocytes and growing lymphoblasts. Inhibition of protein synthesis abolished the synergistic effect on mRNA leading to levels similar to those observed in cells treated with mitogen alone. Synergistic induction is dependent upon synthesis of protein factors either within the cells or produced as soluble mediators; these factors are not simply lymphokines since addition of exogenous factors to the cultures did not reverse the block on synergy by the inhibition. These data suggest that protein factors though they may be important in exerting qualitative control on the level of production of IFN‐γ have no role in the initial activation of the gene.