bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell help in human antigen‐specific antibody responses can be replaced by interleukin 2
Authors: Callard Robin E. , Smith Susan H. , Shields John G. , Levinsky Roland J. 
Published: February 2007

AbstractRecombinant IL2, and immunosorbent/high performance liquid chromatography‐purified interleukin 2 (IL2) obtained from the human T cell leukemic line Jurkat, but not interferon‐α or ‐γ, were able to substitute for T cells in specific antibody responses to influenza virus by T cell‐depleted (E−) human peripheral blood mononuclear cells, and resulted in antibody formation equivalent to that obtained in the presence of T cells. The antibody response was shown to be antigen specific by using two non‐cross‐reacting strains of influenza virus (A/X31 and B/HK). IL2 in this assay therefore functions as a T cell‐replacing factor. Less than 1 % of T (UCHT1+) cells were present in the E− preparations, and this number did not increase during the 7‐day culture with antigen and IL2. Because the frequency of T helper cells for X31 is known to be less than 5 ± 10−5, this low number of contaminating cells excluded indirect action of IL2 through antigen‐specific T helper cells. Three to four times less IL2 was required for antibody production by E− cells than was needed for optimal proliferation by an IL2‐ dependent T cell line. Moreover, the concentration of anti‐Tac required for 50% inhibition of the IL 2‐induced antibody response was 50 times less than required for 50% inhibition of IL2‐dependent proliferation by the T cell line. But when T cells were added back to the E− cells, the anti‐Tac inhibition curve shifted back to that obtained with the T cell line. In cell labeling experiments, Leu11+ cells but not HNK1+ cells were increased in E− cells cultured with antigen and IL2. This increase in Leu 11+ cells was abolished by prior passage of the E− cells through Sephadex G‐10 columns without affecting the IL2‐induced antibody response. From these experiments we conclude that IL2 can replace T cells in specific antibody responses, and that the IL 2 effect is not mediated indirectly through T cells or large granular lymphocytes.
Interaction of periodate‐oxidized target cells and cytolytic T lymphocytes: a model system of “polyclonal MHC recognition”
Authors: Keren Zvi , Berke Gideon 
Published: February 2007

AbstractIn oxidation‐dependent cytotoxicity (ODCC), cytolytic T lymphocytes (CTL) non‐specifically recognize, bind to and lyse oxidized target cells (O‐TC) but the precise mechanism whereby CTL react with O‐TC is far from clear (Berke, G., Immunol. Rev. 1983. 72: 5). Here we present evidence that CTL/O‐TC interactions are blocked by aldehyde‐reactive reagents such as hydroxylamine, adipic acid dihydrazide and thiocarbohydrazide and that preformed CTL/O‐TC conjugates dissociate upon reduction with NaBH4, suggesting that active aldehyde groups of O‐TC rather than intercellular Schiff bases are involved in the recognition and lysis of O‐TC by CTL in ODCC. The aldehydes are bound to trypsin‐sensitive, non‐H‐2 glycoproteins that appear to be different and unique in the three different target cell lines so far examined (EL4, L1210, R1.1). In view of these and previous findings we would like to suggest that in ODCC, active aldehydes react with adjacent major histocompatibility complex and perhaps other cell‐surface molecules to create a multitude of modified conformations, responsible for the “polyclonal” (nonspecific) MHC recognition and lysis of O‐TC by CTL, as well as for an altered pattern of H‐2 antibody binding to O‐TC.
Anti‐CD2 (sheep red blood cell receptor) monoclonal antibodies and T cell activation I. Pairs of anti‐T11.1 and T11.2 (CD2 subgroups) are strongly mitogenic for T cells in presence of 12‐O‐tetradecanoylphorbol 13‐acetate
Authors: Olive Daniel , Ragueneau Marguerite , Cerdan Chantal , Dubreuil Patrice , Lopez Marc , Mawas Claude 
Published: February 2007

AbstractA large collection of monoclonal antibodies (mAb) directed against sheep red blood cell (SRBC) receptor (cluster of differentiation 2 : CD2) were classified according to three criteria: (a) their inhibitory effect on T cell‐SRBC rosette formation; (b) the epitopic cluster recognized on the CD2 molecule; (c) their reactivity with resting or activated T cells. All mAb were then tested in a two by two checkerboard fashion for possible T cell mitogenicity, in presence or absence of a submitogenic dose of 12‐O‐tetra‐decanoylphorbol 13‐acetate (TPA), an agent known to be comitogenic for T cells, presumably in delivering a second signal, usually accessory cell dependent. The combined data demonstrate that in the absence of TPA only few pairs of mAb directed at distinct epitopes of the CD2 molecule were mitogenic for T cells (in approximately 30% of the population tested), and in the presence of a submitogenic dose of TPA the majority of T11.1 anti‐CD2‐mAb (9 out of 11) were strongly mitogenic for T cells of all individuals tested when paired with T11.2 anti‐CD2 mAb. The two anti‐T11.1 mAb, noncomplementary to anti‐T11.2 mAb, were, however, strongly mitogenic when added to mAb of the T11.3 subgroup, represented by 1‐Mono‐2A6.Taken together, these data strongly suggest that the main characteristic of T cell mitogenesis triggered by anti‐CD2 mAb is the requirement for a signal delivered simultaneously to two different epitopes of the CD2 molecule, whether these epitopes are T11.1, T11.2 or T11.3.
Detection of rearranged T cell receptor β‐chain gene and induction of cytolytic function in interleukin 2‐ responsive day 14–15 murine fetal thymocytes
Authors: Hardt Conny , Fleischer Sabine , Steinmetz Michael , Wagner Hermann 
Published: February 2007

AbstractA subpopulation of interleukin 2 (IL 2) receptor‐positive day 14–15 murine fetal thymocytes can be induced by recombinant IL 2 to proliferate over prolonged time periods in dissociated cell cultures. The proliferating day 14–15 fetal thymocytes exhibit no cytolytic effector function, nor do they rearrange T cell receptor β chain genes. This contrasts with thymic organ cultures in which day 14–15 thymocytes do rearrange β chain genes and give rise to immunocompetent cells. However, such events can also take place in dissociated cell cultures, provided the IL 2‐responsive thymocytes are cultured on syngeneic feeder cells in the presence of IL 2 and the mitogen concanavalin A. Under such conditions rearrangement of the β chain gene complex becomes detectable and cytolytic effector cells are generated. The frequency of inducible cytolytic precursor cells in day 14–15 thymocytes is 1/7000. These data either imply that immunocompetent cells are already present in the day 14–15 fetal thymus, or differentiation from precursors to immunocompetent cells must occur in dissociated cell cultures.
Interleukin 2 is a proliferative signal for B cells from autoimmune mice
Authors: Lehmann Kathrin R. , Kotzin Brian L. , Portanova Joseph P. , Santoro Thomas J. 
Published: February 2007

AbstractT cells from murine lupus strains manifest complex defects in interleukin 2 (IL 2) production and receptor expression. The capacity of B cells from such mice to utilize IL2 as a growth factor has not been previously reported and is examined herein. Anti‐Thy‐1.2 plus complement‐treated spleen cells from 6–8‐week‐old autoimmune MRL‐ Ipr/lprmice and from age and sex‐matched immunologically normal CBA/J mice were cultured with lipopolysaccharide (LPS) for 36 h and analyzed for the expression of IL 2 receptors using the monoclonal antibody 7D4. The percentage of B cells expressing IL2 receptors was comparable in MRL‐lpr/lpr and CBA/J mice. In contrast to those from CBA/J, BALB/c and (BALB/c × NZW)F1 mice, LPS‐stimulated B cells from MRL‐lpr/lpr and from (NZB × NZW)F1 mice were capable of proliferating in response to IL 2. Fractionation of MKL‐lprl/lprB cells using Percoll gradient density separation demonstrated that the IL2‐responsive population consisted predominantly of large cells. In addition, unfractionated B cells from MRL‐lpr/lpr mice were found to be substantially more responsive to IL2 than those from CBA/J and BALB/c mice following activation with anti‐immunoglobulin plus LPS. The hyper‐responsiveness to IL 2 may be a consequence of the state of activation of autoimmune B cells and is of potential importance in the pathogenesis of systemic lupus erythematosus.
A comparison of eosinophil‐activating factor (EAF) with other monokines and lymphokines
Authors: Thorne Kareen J. I. , Richardson Brian A. , Taverne Janice , James Williamson D. , Vadas Mathew A. , Butterworth Anthony E. 
Published: February 2007

AbstractMonocytes from moderately eosinophilic individuals secrete material that enhances the cytotoxic activity of eosinophils against antibody‐coated schistosomula of Schistosoma mansoni. This material is not a single substance, but can be fractionated into several active components of different size and different charge. Gel filtration of mononuclear cell supematants separated the eosinophil‐activating activity into a major component of molecular mass of 40 kDa and a minor component of molecular mass of < 10 kDa. The major component exhibited further heterogeneity on fractionation by high performance liquid chromatography. The bulk of the eosinophil‐activating activity could be separated from both colony‐stimulating factor (CSF)α activity and from tumor necrosis factor (TNF) activity. However, human recombinant CSFα (GM‐CSF), human recombinant TNF and rabbit tumor necrosis serum all had eosinophil‐activating activity when tested against schistosomula. Eosinophils were not activated by interleukin 1, interleukin 2, interferon‐α, lipopolysaccharide or phorbol myristate acetate.
T cell clones which share T cell receptor epitopes differ in phenotype, function and specificity
Authors: Yssel Hans , Blanchard Dominique , Boylston Art , De Vries Jan E. , Spits Hergen 
Published: February 2007

AbstractRecently, we described a monoclonal antibody (3D6) that reacts with the T cell receptor (Ti) of the T leukemic cell line HPB‐ALL and that cross‐reacts with 2–10% of the T cells of normal healthy individuals. In this study we report the establishment of T cell clones that are 3D6+ but that differ in function and phenotype. These clones were established according to two different protocols: (a) T cells of donor HY (10% 3D6+) were stimulated with the Epstein‐Barr virus‐transformed cell line JY. The proliferating 3D6+ T cells were enriched using a rosetting technique and cloned, (b) T cells of donor HY were stimulated with the 3D6 antibody and subsequently expanded in recombinant interleukin 2‐containing medium. This yielded 70% 3D6+ T cells which after activation with either Daudi cells or with TT in the presence of autologous non‐T cells, followed by cloning, resulted in antigen‐specific 3D6+ T cell clones. The 3D6+ T cell clones were also tested on their reactivity with 4 other monoclonal antibodies (1C1, 1C2, 2D4, 65) specific for the Ti of HPB‐ALL. The antibodies 1C1 and 1C2 reacted with all 3D6+ T cell clones and recognize probably the same epitope as 3D6. The antibodies 2D4 and 65 reacted with two mutually exclusive subsets of T cell clones. All the anti‐Ti antibodies reacted with functional epitopes, since they were able to block the function of the T cell clones. The specificity of the clones was investigated by blocking studies using monoclonal antibodies specific for different major histocompatibility complex antigens. No correlation was found between the expression of the different Ti epitopes and the specificity, the CD4/CD8 phenotype or function of the clones.
A lymphoid cell surface glycoprotein involved in endothelial cell recognition and lymphocyte homing in man
Authors: Jalkanen Sirpa T. , Bargatze Robert F. , Herron Lynne R. , Butcher Eugene C. 
Published: February 2007

AbstractWe describe a 90‐kDa lymphocyte surface glycoprotein, recognized by the monoclonal antibody Hermes‐1, that is involved in endothelial cell recognition and lymphocyte trafficking in man. This molecule (a) is selectively expressed on normal or transformed lymphoid cells that are able to recognize and bind to high endothelial venules (HEV, specialized vessels that mediate lymphocyte exit from the blood into lymphoid organs); (b) appears to be linked to HEV recognition function since, in fluorescence‐ activated cell sorting of variants of a cloned cell line, HEV binding ability co‐selects with the Hermes‐1 antigen; (c) bears the predominant cell surface epitopes recognized by heterologous anti‐human lymphocyte antibodies able to interfere with lymphocyte binding to HEV; and (d) is structurally similar to a previously described mouse lymphocyte surface receptor for HEV. These findings demonstrate that the molecule defined by Hermes‐1 either functions as a specific lymphocyte surface receptor for HEV, or is both precisely coregulated and physically and/or functionally associated with such receptors. The expression of this putative receptor for HEV on normal human lymphocyte populations parallels, and thus presumably helps determine, their migratory status in vivo. Hermes‐1 should be a powerful tool for analyzing the role of endothelial cell recognition in the traffic of normal and neoplastic human lymphocytes.
Control of cell proliferation within the human thymus. A very limited thymocyte subpopulation generates a suppressive activity
Authors: Gelin Catherine , Boumsell Laurence , Bernard Alain 
Published: February 2007

AbstractIt is shown here that a minor subpopulation of the human thymus, representing 2–3% of the whole thymocyte population, can suppress proliferation of syngeneic or allogeneic thymocytes to various stimuli. In contrast, this suppressor cell population has no influence on the proliferative response of peripheral blood lymphocytes. This subpopulation was defined by its cell surface phenotype as CD3+, CD1−, 4−, 8− cells. Its suppressive activity is generated after concanavalin A (Con A) stimulation, but not after stimulation with phytohemagglutinin. In addition, the suppressive activity is not modified by extensive washes of Con A‐stimulated cells with 1‐O‐methyl‐α‐D‐ glucopyranoside, a specific sugar for Con A. This suppressor cell population does not exert any detectable cytotoxic activity, nor does it act by consuming available interleukin 2 (IL2). Rather, it prevents IL2 receptor expression on thymic target cells. Since Con A might activate T cells by binding to molecules physiologicaly involved in T cell activation, particularly the CD3‐T cell receptor complex, these data could be relevant to the regulation of normal thymic differentiation.
Modulation of c‐fos and c‐myc mRNA levels in normal human lymphocytes by calcium ionophore A23187 and phorbol ester
Authors: David Grausz J. , Fradelizi Didier , Dautry François , Monier Roger , Lehn Pierre 
Published: February 2007

AbstractA transient expression of the proto‐oncogenes c‐fos and c‐myc is rapidly induced by growth factors or mitogens in different cell types including lectin‐stimulated lymphocytes. To elucidate the early events of lymphocyte activation, we determined (by Northern blot analysis) the steady‐state levels of c‐fos and c‐myc mRNA in normal human peripheral blood lymphocytes (PBL) stimulated with the Ca2+ ionophore A23187 and/or 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), whose biological activities are well defined. We report that ionophore A23187 (0.5 mUM) or, to a significantly lesser extent, TPA (0.5 ng/ml), neither of which is mitogenic alone at these concentrations, nevertheless can induce a transient accumulation of the protooncogene transcripts. These results indicate that a significant accumulation of c‐fos and c‐myc mRNA can occur without subsequent lymphocyte proliferation. The combination of these two mitogens increases the induced levels of both types of c‐onc mRNAs. The level of mRNA accumulation correlates with the degree of proliferation induced by mitogenic combinations of ionophore A23187 and TPA, as measured by [3H]thymidine incorporation. Thus, these compounds act synergistically both with respect to c‐fos and c‐myc mRNA accumulation and to mitogenicity in human PBL.We also studied the level of c‐fos transcripts following stimulation of the T lymphocyte T3/Ti receptor complex, using monoclonal anti‐T3 antibodies. We observed that mitogenic doses of anti‐T3 also induce an accumulation of c‐fos mRNA, whose induction also is synergized by TPA. These results suggest that transient accumulation of c‐fos‐, as well as c‐myc, mRNA is a normal event of the immune response. They confirm that Ca2+ ionophore combined with TPA can mimic some molecular features of the early steps of normal human PBL activation.
Role of the major histocompatibility complex in targeting effector T cells into a site of virus infection
Authors: Doherty Peter C. , Allan Jane E. 
Published: February 2007

AbstractBone marrow radiation chimeras have been used as virus‐infected, cyclophosphamide‐suppressed recipients to analyze the major histocompatibility complex (MHC) restriction constraints on the adoptive transfer of lymphocytic choriomeningitis by immune T cells. The basic protocol employed [(A × B)F1→(A × C)F1] chimeras, where A, B, C are different MHC haplotypes, and the establishment of appropriate chimerism was measured by the capacity of, for instance, the transferred A, T cells to generate MHC‐restricted, virus‐specific cytotoxic T lymphocytes (CTL) in the spleen of the [(A × B)F1 →(B × C)F1] recipients. The experiments show quite clearly that maximal inflammatory process is only induced when donor bone marrow, irradiated recipient and transferred T cells share at least one MHC haplotype. Compatibility of the T cells and the radiation‐resistant phenotype alone in, for instance, transfer of C immune lymphocytes into [(A × B)F1→ (B × C)F1] recipients produced little inflammation if the chimeras had been established for at least 10 weeks. These results are compatible with a model which proposes that the transferred T cells first replicate in MHC‐compatible lymphoid tissue and are then targeted onto the appropriate MHC plus virus expressed on cells in the blood‐cerebrospinal fluid (CSF) barrier. An alternative postulate, that all that is required for the development of inflammatory process is MHC‐restricted T cell replication in lymphoid tissue, with subsequent nonspecific localization to the central nervous system (CNS), was explored by transferring B, immune T cells into [(A × B)F1→ A] recipients. The finding was that H‐2b effectors did not cause any meningitis in [H‐2k×bFl→ H‐2k] recipients, though potent H‐2b‐restricted CTL were generated in the spleens of comparable chimeras. However, in the H‐2k immune → [H‐2k×bF1 → H‐2b] transfer there was evidence of moderate inflammation that was about 9 times less severe than that caused by the H‐2b effectors in comparable recipients. This indicates that, for maximal inflammatory process to occur, the T cells must encounter MHC‐compatible, virus‐infected cells in the CNS, with the effect being absolute in one strain combination and partial in another. Possible mechanisms underlying this divergence are discussed.
Mice naturally tolerant to C5 have T cells that suppress the response to this antigen
Authors: Cairns Lloyd , Rosen Fred S. , Borel Yves 
Published: February 2007

AbstractWe examined whether C5‐sufficient mice which are naturally tolerant to this antigen have suppressor T cells to C5 humoral immune response. Two congenic strains of mice B10.D2 (NSN) and B10.D2 (OSN) differing only in the presence or absence of C5 were used. Irradiated (760 rds) sufficient hosts were reconstituted with a nonadherent spleen cell suspension from either sufficient or deficient mice or a mixture of both. Hemolytic C5 levels were assayed. Sufficient spleen cells appeared to prevent the drop of C5 level caused by anti‐C5 antibody made by deficient spleen cells. Spleen cell suspensions from sufficient mice primed with deficient spleen cells exhibited better anti‐C5 activity than normal sufficient spleen cell suspensions. This anti‐C5 activity is abrogated by treatment of the NSN spleen cell suspensions obtained from NSN primed with OSN spleen cells with anti‐Thy‐1.2 antiserum and complement. Suppression of the humoral response to C5 failed to affect the anti‐sheep red blood cell immune response. Suppressor T cells are resistant to low‐dose irradiation, cortisone treatment and adult thymectomy. In contrast, they are sensitive to high doses of irradiation and both high and low doses of cyclophosphamide treatment. Thus, C5 sufficient mice, in contrast to C5‐deficient mice, appear to have antigen‐specific suppressor T cells which downregulate the humoral immune response to C5.In addition, we examined the relationship of these suppressor T cells to the state of tolerance in helper T cells of C5‐sufficient mice. This was done in irradiated deficient mice which were repopulated with spleen cell suspensions selectively depleted of either Lyt‐l+ or Lyt‐2+ T cell subsets. These chimeras were challenged with murine C5 and both the primary and secondary immune response was measured by inhibition of the C5 hemolytic activity. It was found that only spleen cell suspensions of the deficient mice selectively depleted from the Lyt‐2+ subset of T cells responded to the antigen both in the primary and secondary response. In contrast, either subset of T cells from the sufficient mice failed to respond. Thus, it appears that in sufficient mice helper T cells to C5 are intrinsically tolerant or physically and/or functionally deleted. In conclusion, the data suggest that both T cell compartments are unresponsive and play a role in the mechanism of tolerance to a physiologic antigen.
T cell receptor expression and receptor‐mediated induction of clonal growth in the developing mouse thymus. High surface β‐chain density is a requirement for functional maturity
Authors: Nicholas Crispe I. , Husmann Linda A. , Bevan Michael J. 
Published: February 2007

AbstractThe ontogeny of T cell antigen receptor expression and function in the mouse thymus has been studied using a monoclonal antibody, F23.1, which recognizes a determinant on the β chain of the receptor, and stains 25% of mature T cells and around 7‐15% of adult thymocytes from most mouse strains. The same monoclonal antibody selectively activates Lyt‐2+ peripheral T cells. Receptors are detectable by staining and fluorescence‐activated cell sorter analysis from fetal day 17, and thereafter the overall frequency increases steadily towards adult levels. However, late fetal thymocytes express all of their antigen receptor β chain at a very low level, visible by staining as a “shoulder” on the peak of negative cells. Thymocytes with high‐density surface β chain, visible by staining as a distinct peak, appear only after birth and are a prominent feature at neonatal day 4. In the late fetus, expression of β chain can be detected on thymocytes with the “mature” L3T4−, Lyt‐2+ phenotype. Despite this, F23.1 responsive precursors are not found in the fetal thymus, and appear in two waves, the first during day 1 of postnatal life and the second between days 3 and 4. These data suggest that high‐density surface expression of T cell receptor β chain occurs in parallel with functional maturation.