bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ontogeny of expression of UCHL1 antigen on TcR‐1+ (CD4/8) and TcRδ+ T cells
Authors: Hayward Anthony R. , Lee Jane , Beverley Peter C. L. 
Published: March 2007

AbstractThe frequency of blood mononuclear cells expressing the 180‐kDa splice variant of the common leukocyte antigen identified by the UCHL1 monoclonal antibody (a characteristic of post‐thymic cells which have been through a cycle of stimulation) rose in a logarithmic relationship to age between birth and 16 years. At birth only a low frequency of CD4+ (negative for CD 25) and no CD8+ T cells expressed UCHL1. The subsequent increase in UCHL1 expression occurred in parallel on T cells expressing α/β receptors and γ/δ receptors, suggesting that these subsets participated in postthymic proliferation in proportion to their numbers in blood. The frequency of UCHL1 expression on CD8 cells was 5–15% less than on CD4 cells.
Interleukin 7 (murine pre‐B cell growth factor/lymphopoietin 1) stimulates thymocyte growth: regulation by transforming growth factor beta
Authors: Chantry David , Turner Martin , Feldmann Marc 
Published: March 2007

AbstractThe effects of interleukin 7 (IL 7) previously known as murine pre‐B cell growth factor/lymphopoietin 1 on the growth of murine thymocytes was investigated. In the presence of a suboptimal dose of phytohemagglutinin, IL 7 induced a dose‐dependent increase in thymocyte proliferation which was comparable to that induced by IL 1. Additionally IL 7 was shown to synergize with a suboptimal dose of IL 1 to enhance thymocyte proliferation. Thymocyte proliferation induced by IL 7, like that induced by IL 1, was inhibited when either recombinant transforming growth factor (TGF) β1 or β2 were added at the initiation of culture. Interestingly, IL 7‐driven thymocyte proliferation was considerably less susceptible to inhibition by TGF‐β1 or TGF‐β2 than that induced by IL 1. Taken together these results suggest IL 7 may activate distinct populations of thymocytes and/or act through a pathway distinct from that utilized by IL 1.
Antibodies against the T cell receptor/CD3 complex interfere with distinct intra‐thymic cell‐cell interactions in vivo: correlation with arrest of T cell differentiation
Authors: Kyewski Bruno A. , Schirrmacher Volker , Allison James P. 
Published: March 2007

AbstractPostnatal treatment of mice with antibodies against the T cell receptor complex (TcR) prevents the differentiation of mature T cells in the thymic medulla without affecting the generation of most immature cortical thymocytes, thus interfering with a discrete stage of intra‐thymic T cell differentiation at the cortex/medulla transition. This result has been interpreted as indicating a direct role of the TcR in the differentiation of immature to mature T cells, possibly via TcR‐ligand interactions during direct cell‐cell contact. Here we analyze the effect of anti‐TcR (Vβ8 family) and anti‐CD3 (ε chain) antibodies on distinct intra‐thymic cell‐cell interactions in vivo. We find that the maturation arrest of thymocytes correlates with a nearly complete abrogation of interactions of corresponding immature thymocyte with I‐A/E+ cortical epithelial cells and I‐A/E+ medullary dendritic cells, while preserving interactions with adherent I‐A/E− macrophages. It is proposed that the blockade of thymocyte‐epithelial cell recognition in the cortex by anti‐TcR antibodies prevents the translocation of thymocytes into the medulla and their subsequent differentiation and selection, including interactions with dendritic cells. Interestingly, the anti‐CD3 mAb treatment seems to spare the intra‐thymic development of the CD3+, CD4−/CD8− T cell lineage.
Human T cell activation: differential response to anti‐CD28 as compared to anti‐CD3 monoclonal antibodies
Authors: Bjorndahl Jay M. , Sung Sun‐Sang J. , Hansen John A. , Fu Shu Man 
Published: March 2007

AbstractMonoclonal antibodies (mAb) against CD3 or CD28 in conjunction with the tumor promoter phorbol 12‐myristate 13‐acetate (PMA) induce interleukin 2 receptor (IL 2R) expression, IL 2 production and proliferation in resting T cells. Recent studies indicate that these two pathways are biochemically distinct. In this study T cell activation induced by PMA and anti‐CD28 mAb 9.3 is compared to the effects of PMA plus anti‐CD3 mAb (T3‐II and 235) in the presence or absence of cyclosporin A (CsA), dibutyryladenosine 3′ : 5′ cyclic monophosphate (db‐cAMP) or cholera toxin (CT). Proliferation of T cells stimulated with PMA plus mAb 9.3 is resistant to the inhibitory effects of CsA, db‐cAMP and CT. Only at the highest dose did CsA have any effect on PMA plus mAb 9.3‐induced T cell proliferation. Conversely, CsA, db‐cAMP and CT inhibit PMA plus T3‐II‐induced T cell proliferation. mRNA analysis further demonstrates the similarities and the differences between the CD28 and CD3 activation pathways. Recently, T3‐II was reported to induce tumor necrosis factor (TNF) and lymphotoxin (LT) mRNA synthesis in PMA‐treated T cells. In this study mAb 9.3 is shown to substitute for T3‐II in the induction of TNF and mRNA. However, the production of TNF and LT mRNA in PMA plus mAb 9.3‐treated T cells is greater than that seen in PMA plus T3‐II‐treated cells. mRNA synthesis included by PMA plus T3‐II is blocked by CsA. mRNA production in T cells activated with PMA plus mAb 9.3 is resistant to CsA. Similar results are noted with IL 2 and IL 2R mRNA. Flow cytometric analysis of the IL 2R confirms the mRNA data. CsA blocks the T3‐II‐induced potentiation of PMA‐induced IL 2R expression but not the mAb 9.3‐induced potentiation. This differential inhibitory effect of CsA on IL 2R expression is also seen with db‐cAMP and CT. We examined the effects of these two pathways on the expression of the early activation antigen EA 1 and cytoplasmic free calcium. Recently, we have shown anti‐CD3 mAb potentiate EA 1 expression induced by 1,2‐sn‐dioctanoylglycerol and this potentiation is calcium dependent, dp‐cAMP blocks T3‐II‐ and 235‐induced potentiation of EA 1 expression and inhibits the T3‐II‐ and 235‐mediated rise in intracellular free calcium ([Ca2+]i). Conversely, 9.3 does not potentiate EA 1 expression or induce a rise in [Ca2+]i. These results provide further evidence that the CD28 and CD3 activation pathways utilize distinct signal transduction pathways.
Peripheral T lymphocytes: expansion potential and homeostatic regulation of pool sizes and CD4/CD8 ratios in vivo
Authors: Rocha Benedita , Dautigny Nicole , Pereira Pablo 
Published: March 2007

AbstractPeripheral T lymphocytes are self‐renewable cell populations since, when transferred into syngeneic T cell‐deficient athymic mice, they expand in the absence of exogenous antigen stimulation. Quantification of the expansion potential of CD4+ cells by transfer of the same population into successive host mice shows that these cells are able to divide up to 56 times in vivo. Therefore, as a population, CD4+ cells can increase in size 8 × 105‐fold, an expansion potential of similar magnitude to that previously reported for colony‐forming units. Injection of different numbers of T cells at different CD4/CD8 ratios is followed by T cell accumulation to a similar plateau in recipient nude mice. This indicates that peripheral T lymphocytes are tightly regulated by homeostatic mechanisms that control pool sizes and CD4/CD8 ratios, in a manner independent of the cell input into the peripheral compartment. This kinetic behavior of mature T cells permits the maintenance at the periphery of any T cell specificity previously selected in the thymus. The expansion capacity of peripheral T cells may also allow extensive modulation of peripheral T cell specificities, which would confer a major role to post‐thymic selection of mature peripheral T cell repertoires.
Interleukin 4 strongly augments or inhibits DNA synthesis and differentiation of B‐type chronic lymphocytic leukemia cells depending on the costimulatory activation and progression signals
Authors: Carlsson Mats , Sundström Christer , Bengtsson Mats , Tütterman Thomas H. , Rosén Anders , Nilsson Kenneth 
Published: March 2007

AbstractThis study describes the opposing effects that interleukin (IL) 4 exerts on the B cell stimulatory factor (BSF‐MP6) and IL 2‐dependent proliferation and differentiation of cells of one selected B‐type chronic lymphocytic leukemia cell clone (I83), which depend on the nature of the activation inducer. In I83 cells activated by a 1‐h pulse of 12‐O‐tetradecanoylphorbol 13‐acetate, the BSF‐MP6‐dependent DNA synthesis was strongly enhanced by 50–100 U/ml of recombinant IL 4. Recombinant IL 2 stimulation was necessary only when a suboptimal dose of BSF‐MP6 was used. The differentiation was also markedly enhanced by IL 4 as measured by quantitation of IgM secretion both at the population (enzyme‐linked immunosorbent assay analyses of the supernatant) and single‐cell level (enzyme‐linked immunospot technique), by morphological examination of the maturation stage and flow cytometric analysis of differentiation‐associated surface antigens (CD11c, FMC7, PCA‐1 and CD38). No Ig isotype switch was found. In contrast, DNA synthesis and differentiation of I83 cells, activated by Staphylococcus aureus Cowan strain I (SAC) and co‐stimulated with BSF‐MP6 plus IL 2, were strongly inhibited by IL 4, both when it was added simultaneously with SAC or after 2 days of SAC exposure. Analysis of the cell‐cycle progression of SAC and BSF‐MP6 plus IL 2 and IL 4‐stimulated cells by acridine orange staining and fluorescence‐activated cell sorter (FACS) analysis demonstrated an arrest of a minor cell population in G0 and a block of the transition of G1 cells to S phase. Neither the enhancing nor the inhibitory effect of IL 4 on the proliferation and differentiation of I83 cells was an indirect effect via IL 4‐induced activation of contaminating T cells, monocytes or natural killer cells, as shown by experiments where these cell types were depleted by FACS sorting. Furthermore the expression of CD23 and CD25 was not inhibited by IL 4. The results thus demonstrate contrasting biological effects of IL 4 on clonal leukemic B cells depending on the nature of the activation and progression stimuli. This adds to the emerging picture of a very complex cytokine and cell‐to‐cell contact‐mediated regulation of the activation and subsequent growth and/or differentiation of human B cells.
Collagen receptor on T lymphocytes and the control of lymphocyte motility
Authors: Arencibia Ignacio , Sundqvist Karl‐Gösta 
Published: March 2007

AbstractHuman lymphocytes, freshly isolated from blood, were allowed to settle on surfaces coated by collagen type 1, fibronectin, laminin, IgG or albumin at different concentrations. In separate cultures the lymphocytes were also exposed to these proteins in soluble form. The lymphocytes, predominantly T cells, attached to two‐dimensional collagen substrata both in the presence and absence of serum but did not adhere or adhered poorly to substrata coated with fibronectin, laminin, IgG and albumin. In contrast, T blasts induced in a mixed lymphocyte culture adhered to fibronectin‐coated substratum. During contact with substratum‐bound collagen for a 24‐h period, 47 ± 15% of the freshly purified lymphocytes from separate individuals developed motile behavior whereas 16 ± 4% of the cells became motile on fibronectin. Gelatin (denatured collagen) also mediated attachment of lymphocytes to surfaces but only at comparatively high concentrations (40 mg/ml). Collagen and gelatin in solution also caused agglutination and motility of the vast majority of freshly isolated T lymphocytes whereas fibronectin and other proteins, when presented in soluble form, did not. Cell agglutination was maximal at moderate (10 or 20 mg/ml) and cell motility at low gelatin concentrations (1 to 10 mg/ml). High gelatin concentrations (20 and 40 mg/ml) did not induce motile behavior. Cytochalasin B augmented the proportion of adherent cells on gelatin‐coated substrata. In the presence of cytochalasin B gelatin mediated substrate‐adhesion at concentrations below those which normally induced adhesion indicating that motile behavior counteracted persistent lymphocyte adhesion to the substratum. Noteworthy, gelatin/collagen is unique among ligands (e.g. plasma fibronectin and other serum proteins) in its capacity to induce motility in the vast majority of resting lymphocytes freshly isolated from blood within a relatively short period. Taken together these results indicate that circulating lymphocytes have a collagen/gelatin‐binding plasma membrane component. Cross‐linking of this component is a likely explanation for the selective inducing effect of gelatin and collagen on lymphocyte motility. The present results showed that the lymphocyte plasma membrane contains collagen‐binding components with a relative molecular mass of 130 and 55 kDa. The 55‐kDa component also reacted with an anti‐fibronectin antibody. Thus, interactions with the extracellular matrix may control lymphocyte locomotor capacity.
Expression of CD5, a lymphocyte surface antigen on the endothelium of blood vessels
Authors: Gogolin‐Ewens Kathryn , Meeusen Els , Lee Chee‐Seong , Brandon Malcolm 
Published: March 2007

AbstractCD5 is a lymphocyte surface antigen considered to be a pan‐T cell marker although it is also expressed on a small population of B cells. In this report we present evidence that four different monoclonal antibodies specific for the CD5 antigen also recognize a molecule present on the endothelium of blood vessels in certain regions (placentomes) of the pregnant sheep uterus. The identity of the CD5 antigen on the endothelium with that expressed on T lymphocytes was confirmed by molecular mass analysis of the CD5 antigen in membrane extracts of lymphocytes, thymocytes and placentomes which showed that all three antigens have an apparent molecular mass of 67 kDa. Possible implications of this finding in relation to the function of the CD5 molecule and lymphocyte migration are discussed.
Alpha‐globulins suppress human leukocyte tumor necrosis factor secretion
Authors: Scuderi Philip , Dorr Robert T. , Liddil James D. , Finley Paul R. , Meltzer Paul , Raitano Arthur B. , Rybski James 
Published: March 2007

AbstractThe secretion of tumor necrosis factor (TNF) by human peripheral blood mononuclear cells was suppressed by either whole human plasma α‐globulins or purified α1 acid‐glycoprotein, α1‐antitrypsin and α2‐macroglobulin in a concentration‐dependent manner. α1‐Antitrypsin was found to be the most suppressive of the purified proteins tested and completely blocked TNF release at concentrations above 1.25 mg/ml. Both α1‐acid glycoprotein and α1‐antitrypsin blocked TNF secretion by leukocytes which were simultaneously stimulated with either recombinant human interferon‐γ (IFN‐γ) or lipopolysaccharide (LPS). IFN‐γ and LPS‐activated cells were also susceptible to suppression mediated by these two α‐globulins and the inhibition produced by 5 mg/ml α1‐antitrypsin was greater than that caused by either 1 m̈M prostaglandin E2 or 10 ng/ml transforming growth factor‐pi. The level of TNF mRNA in TNF‐secreting and α‐globulin‐suppressed cells was examined and found to be equal in both groups. The suppressive effect of whole α‐globulins was confined to the inhibition of TNF secretion and these plasma proteins had no effect on the cytolytic activity of the recombinant cytokine as measured on murine L‐929 target cells. Thus the α‐globulins, which are a major fraction of the circulating plasma proteins, may function in TNF homeostasis by controlling TNF secretion without inhibiting the biological activity of the released cytokine.
The influence of cyclosporin A on the alternative pathways of human T cell activation in vitro
Authors: Bloemena Elisabeth , Van Oers Rien H. J. , Weinreich Stephanie , Stilma‐Meinesz Anneke P. , Schellekens Peter T. H. A. , Van Lier René A. W. 
Published: March 2007

AbstractTo gain further insight into the mechanism of action of the immunosuppressant cyclosporin A (CyA), we investigated the influence of CyA on proliferative responses of human T lymphocytes, induced via different membrane molecules. As was previously shown, activation of T cells via the T cell receptor (Ti)/CD3 complex with an anti‐CD3 monoclonal antibody was inhibited by CyA. Likewise, triggering of T lymphocytes via the alternative, CD2(T11)‐mediated pathway of activation was strongly inhibited. In contrast, responses induced by phorbol myristate 13‐acetate (PMA; 100 ng/ml) or the combination of an anti‐CD28 monoclonal antibody and a suboptimal concentration of PMA (1 ng/ml) were found to be insensitive to CyA. CyA‐induced inhibition of both anti‐CD3 and anti‐CD2‐mediated proliferation could not be reversed by addition of either PMA (1 ng/ml) or anti‐CD28.An increase in the intracellular free Ca2+ concentration ([Ca2+]i) is an early event observed after stimulation of T cells via CD3 or CD2, whereas stimulation with PMA and anti‐CD28 does not lead to a rise in [Ca2+]i This suggests that the inhibitory action of CyA is related to Ca2+‐dependent signaling pathways. Since we observed that CyA does not interfere with anti‐CD3‐ or anti‐CD2‐induced increases of [Ca2+]i, our data suggest that CyA‐mediated inhibition is related to a later event in these intracellular signaling pathways.
Restricted idiotypic profile of anti‐phosphorylcholine antibodies induced by carrier‐specific helper T cell clones
Authors: Strickland Faith M. , Cerny Jan , Currier Patricia , Infante Anthony J. 
Published: March 2007

AbstractThe primary antibody response of C57BL/6 mice to phosphorylcholine (PC) is dominated by immunoglobulins of the T15 idiotype family. Using monoclonal antibodies that define individual idiotopes (Id) of T15, it has been shown that the antibody plaque‐forming cells (PFC) arise from heterogeneous population of B cells that may express some but not all T15 Id. In the present study, we tested the ability of antigen (keyhole limpet hemocyanin, KLH)‐specific CD4+ T cell clones (Th) to provide help for various T15 B cell subsets in response to PC‐KLH in vitro. Four independently derived, KLH‐specific Th clones were found to provide quantitative help (80–120 PFC/culture of 106 B cells) which was comparable to KLH‐primed, unselected T cells. However, the response in the presence of the cloned T cells was idiotopically restricted: T15 idiotopes B24–44 and B36–75 were expressed on 60% to 90% PFC, whereas Id AB1–2 and B36–82 were not present (0%–20% PFC). All of these Id were highly expressed in cultures with KLH‐primed, unselected splenic T cells. Evidently, the cloned Th cells provided help to only a subset of idiotypically distinct B cells. Bulk spleen T cells from unprimed donors by themselves did not provide any help for the primary response to PC‐KLH. However, when these cells were added to the cultures containing B cells and KLH‐specific Th clones, the repertoire of the response was fully restored, including the AB1–2/B36–82 Id (50%–80% PFC). These results suggest the existence of an auxiliary helper mechanism that may be required for activation of some B cells in addition to the antigen‐specific Th cells.
Interleukin 6 stimulates synthesis of complement proteins factor B and C3 in human skin fibroblasts
Authors: Katz Yitzak , Revel Michel , Strunk Robert C. 
Published: March 2007

AbstractHuman interleukin (IL) 6 is a multifunctional cytokine which is synthesized by fibroblasts in response to many stimuli, including bacterial lipopolysaccharide (LPS). During acute‐phase response, liver cells secrete a specific group of proteins among which components of the complement system and IL 6 appear to be an important mediator of this response. Human skin fibroblasts also synthesize at least seven proteins of the complement system. Each of these seems to be characteristically regulated by soluble mediators of the inflammatory process. Here we report that in fibroblasts, IL 6 induces increases in the rate of synthesis of factor B and C3, activator proteins of the alternative pathway of complement activation. The increases in factor B and C3 were concentration dependent reaching about 40‐ and 15‐fold, respectively. The protein increases were observed within 4 h after IL 6 addition to the cells and were accompanied by increase in factor B and C3 mRNA. The data suggest that the induction of factor B and C3 by LPS may be mediated, at least in part, by IL 6 induced by LPS. This new function of IL 6 could provide a local protection against invading agents through activation of the antibody‐independent alternative pathway of complement activation.
Both virgin and memory T cells cluster with dendritic cells during autologous and allogeneic mixed leukocyte reaction
Authors: Vakkila Jukka 
Published: March 2007

AbstractThe T cell population is comprised of two distinct reciprocal subsets identifiable by UCHL1 and 2H4 antibodies. 2H4+ cells are virgin T cells and UCHL1+ cells are memory T cells. Previously it has been shown that dendritic cells (DC) form clusters with T cells. In this study we have examined the proportions of UCHL1+ and 2H4+ T cell subtypes in DC‐T cell clusters. DC and T cells were purified from human peripheral blood and cultured in autologous or allogeneic combinations. Clusters, which were visible after culture for 24–48 h, were separated and the phenotype of the cells in the clusters was analyzed. It was found that the ratio of UCHL1+ and 2H4+ cells was the same among both clustered and nonclustered cells. Autologous clusters contained the same proportions of UCHL1+ and 2H4+ cells as allogeneic clusters. Experiments with separated UCHL1+ and UCHL1− T cells demonstrated that in autologous mixed leukocyte reaction mainly UCHL1− cells proliferated. Separated clusters were cultured for a total period of 7 days, which demonstrated that the majority of the T cells derived either from autologous or allogeneic clusters were UCHL1+ activated blasts. The remaining 2H4+ T cells resembled inactivated T cells. Thus it is concluded that the initial binding of T cells to autologous or allogeneic DC is mediated by a mechanism which is unaffected by the differentiation of virgin T cells into memory T cells. The low proliferative response of memory T cells to autologous DC suggested that clustering with DC does not necessarily lead to proliferative activity. Autoreactive T cells do not differ from alloreactive cells in acquiring the antigenic phenotype of memory T cells after activation.