bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell interactions generated by synthetic peptides covalently linked to a carrier
Authors: Childerstone Amanda , Haron Jay A. , Lehner Thomas 
Published: March 2007

AbstractWe have attempted to extend the synthetic peptide‐carrier bridge concept of T cell‐B cell interaction to T cell‐T cell interaction. DNA synthesis of human CD4 cells that were sensitized in vivo to a native streptococcal antigen (SA) was stimulated in vitro with synthetic peptides (SP) derived from the sequence of native SA. The SP were linked to tetanus toxoid (TT) as a carrier which was recognized by primed T cells. The uptake of [3H]thymidine was significantly greater when stimulated with covalently linked SP‐TT than that with non‐covalently mixed SP and TT. The TT‐ and SP‐sensitized CD4 cells were then enriched and depleted by panning on TT‐ or SP‐treated monocyte layers. When TT‐enriched CD4 cells were reconstituted with SP‐enriched cells, [3H]thymidine uptake was significantly greater with the linked SP‐TT than with the mixed SP and TT. However, reconstitution of the TT‐enriched with SP‐depleted CD4 cells or the converse failed to increase significantly DNA synthesis by cells stimulated with the linked SP‐TT. The production of interleukin 2 (IL2) and expression of IL2 receptors were then assayed to examine any difference in stimulation between TT and SP. Both IL 2 and IL 2 receptors were diminished and delayed when T cells were stimulated with SP as compared with TT. The results suggest that epitope‐linked clusters of monocytes, TT‐sensitized CD4 and SP‐sensitized CD4 cells enable IL 2 released by the TT‐sensitized CD4 cells to stimulate the SP‐sensitized CD4 cells that produce inadequate amounts of IL 2. Indeed, addition of recombinant IL 2 to T cells stimulated with mixed SP and TT induces an increase in DNA synthesis which becomes similar to that resulting from stimulation with the linked SP‐TT.
Differential secretion of tumor necrosis factor‐α and granulocyte/macrophage colony‐stimulating factors but not interferon‐γ from CD4 compared to CD8 human T cell clones
Authors: Pawelec Graham , Schaudt Kurt , Rehbein Arnika , Busch Friedrich W. 
Published: March 2007

AbstractTumor necrosis factor‐alpha (TNF‐α) is a pleiotropic lymphokine which may have important regulatory effects on immune responses. It is shown here that eight alloreactive CD4 T cell clones (TCC) secreted significant amounts of TNF‐α after stimulation with either specific alloantigen or 12‐O‐tetradecanoylphorbol 13‐acetate together with the calcium ionophore ionomycin (up to 50 ng/ml/24 h/106 cells) whereas CD8 TCC failed to do so (max. 2 ng/ml/24 h/106 cells). The CD8 TCC also secreted markedly less granulocyte/macrophage colony‐stimulating factor than the CD4 cells. However, this was not indicative of a general decrease of lymphokine production by CD8 cells because CD4 and CD8 TCC both secreted similar amounts of interferon‐gamma. These results show that regulatory CD4 lymphocytes can produce large amounts of TNF‐α, whereas CD8 effector cells cannot do so.
Bu‐1 antigen expression as a marker for B cell precursors in chicken embryos
Authors: Houssaint Elisabeth , Lassila Olli , Vainio Olli 
Published: March 2007

AbstractGenetically polymorphic cell surface antigen, Bu‐1, is expressed on B cells as well as on a subset of macrophages. Bu‐1 cells are also present in embryonic spleen and bone marrow, and these could represent prebursal precursors for B cells and Bu‐1 macrophages. To test the repopulation capacity of these cells we sorted 14‐day embryonic spleen cells from Bu‐1a‐homozygous donors into Bu‐la and Bu‐la‐ fractions and transferred them into age‐matched irradiated Bu‐1b‐homozygous recipients. Four to six weeks after hatching, the recipients were analyzed for Bu‐1 chimerism. The results demonstrate that B cell precursors are exclusively present in the Bu‐1 population of 14‐day embryonic spleen, whereas the Bu‐1 macrophage subpopulation can be repopulated by either the Bu‐1 or the Bu‐1‐ fraction of these embryonic cells. Bone marrow cells from young chickens could also repopulate the Bu‐1 macrophage subset but not the B cell compartment, thus confirming previous data that postnatal bone marrow does not contain B cell precursors. These results demonstrate that all B cell precursors in the 14‐day embryonic spleen carry the Bu‐1 antigen, and suggest that there is no lineage relationship between the Bu‐1 B cells and macrophages.
Surface expression of the T cell receptor complex requires charged residues within the α chain transmembrane region
Authors: John Susan , Banting George S. , Goodfellow Peter N. , Owen Michael J. 
Published: March 2007

AbstractThe T cell receptor (TcR) complex is a multi‐subunit glycoprotein comprising at least five transmembrane polypeptides. An unusual characteristic of each of the trans‐bilayer domains is the presence of charged amino acids. To examine the importance of these residues for the association and consequent surface expression of the components of the complex, a TcR α chain containing either charged or neutral residues within its transbilayer segment was introduced into the human T cell line MOLT‐4, and the appearance of the TcR complex at the cell surface was assayed. Surface expression was observed only in MOLT‐4 cells transfected with the α chain containing charged transbilayer residues. Thus, these residues most probably play a crucial role in the assembly process.
Immune status of a μ, χ transgenic mouse line. Deficient response to bacterially related antigens
Authors: Lamers Marinus C. , Vakil Meenal , Kearney John F. , Langhorne Jean , Paige Christopher J. , Julius Michael H. , Mossmann Horst , Carsetti Rita , Köhler Georges 
Published: March 2007

AbstractWe have examined the immune repertoire and immune response of a mouse that carries transgenes for a μ heavy chain and ϰ light chain. The expression of these genes is under the regulation of their own controlling elements. The transgenes are expressed early in ontogeny and are easily detectable from day 13 of gestation onwards. The pre‐B cells seem to function normally as they generate IgM‐secreting colonies at normal frequencies. Colonies show predominantly the transgenic specificity. Expression of the transgenes is not limited to B cells since around 10%–20% of peripheral T cells and 50% of thymocytes express the μ transgene as an intracellular protein. Ectopic expression of ϰ was not seen. The spleen size of the transgenic mouse is decreased by around 20%; this reduction is largely caused by a reduction of the B cell pool. Almost all B cells express the transgenes, only 30% co‐express endogenous heavy chain genes and all co‐express endogenous light chain genes. Serum Ig levels for IgM and IgA were normal, 20% of the IgM consist of the transgenic product. Serum IgG levels were decreased. T cell functions (helper and cytotoxic) were normal. Immune responses to conventional antigens were impaired, especially in the early phases of the immune response, but after boosting they were virtually normal, except for IgG3 which remained low. Primary antibody reponses to T cell‐independent antigens of the class II type (bacterially related antigens) were absent, although precursor frequencies for these antigens were within the expected range. The significance of this finding, as it relates to allelic exclusion of Ig genes, is discussed.
T cell malignancy in Richter's syndrome presenting as hyper IgM. Induction and characterization of a novel CD3, CD4‐, CD8 T cell subset from phytohemagglutinin‐stimulated patient's CD3, CD4, CD8 leukemic T cells
Authors: Raziuddin Syed , Assaf Hasan M. , Teklu Bayu 
Published: March 2007

AbstractA patient is described, having Richter's syndrome and immunodeficiency with hyper IgM, who developed suppressor T cell lymphoma (CD3, CD4‐, CD8) following untreated helper‐suppressor T cell chronic lymphocytic leukemia (CD3, CD4, CD8). The neoplastic T cells in both malignancies expressed interleukin (IL) 2 receptors but were deficient in typical CD2 and CD5 pan T antigens. Additionally, a large percentage of malignant lymph node T cells expressed HLA‐DR activation antigens. In vitro immunoglobulin‐production experiments demonstrated that the patient's leukemic blood T cells had an excess helper function for IgM synthesis but a suppressor function for IgG and IgA synthesis by normal B and T cells. The leukemic blood T cells demonstrated a poor response to phytohemagglutinin (PHA). A defect in IL 2 receptor expression was evident in PHA‐stimulated leukemic blood T cells. Of interest was the observation that PHA stimulated the induction of a novel CD3, CD4‐, CD8 T cell subset from patient's CD3, CD4, CD8 leukemic blood T cells. These PHA‐induced CD3, CD4‐, CD8 T cell subsets produced an elevated proliferative response to PHA and concanavalin A, had a helper cell function for IgM synthesis and produced highly elevated amounts of IL 2.
Synergy between interleukin 4 and interleukin 2 conveys resistance to cyclosporin A during primary in vitro activation of murine CD8 cytotoxic T cell precursors
Authors: Bubeck Ruth , Miethke Thomas , Heeg Klaus , Wagner Hermann 
Published: March 2007

AbstractEven though cyclosporin A (CsA) suppresses in vitro production of lymphokines such as interleukin 2 (IL 2) and responsiveness of cytotoxic T cell (CTL) precursors to IL 2, thereby inhibiting the in vitro generation of CTL, in vivo CsA does not affect the induction of alloreactive CTL. This paradox suggests that CsA‐resistant signals are operating in vivo. Using an in vitro model system in which the requirement for antigen‐presenting cells during primary activation of resting murine CD8 T cells is bypassed by immobilized anti‐CD3 monoclonal antibodies, we here describe conditions in which IL 4 conveys CsA resistance to murine CD8 T cells triggered by immobilized anti‐CD3 monoclonal antibodies to respond to IL 2. CsA resistance of IL 4 and IL 2‐responsive CD8 T cell parallels conditions in which signals provided by IL 4 and IL 2 synergize with each other. CsA dissociates in vitro proliferative and differentiative events by suppressing the former while enhancing the latter. In addition to the known pleiotropic effects of IL 4, our results define an IL 4‐dependent, CsA‐resistant signal pathway which allows CTL differentiation in the absence of significant cell proliferation.
Characterization of the subset of immature thymocytes which can undergo rapid in vitro differentiation
Authors: Nikoli¸‐Žugi¸ Janko , Moore Mark W. , Bevan Michael J. 
Published: March 2007

AbstractRecently, we reported that thymocytes expressing the CD8 molecule on their surface can give rise to CD4+CD8+ double‐positive and CD4+ single‐positive progeny following intrathymic transfer into an irradiated host mouse. Thymcoytes expressing a high density of CD8, referred to as CD8hi, and those expressing a low density of the molecule, CD8lo, were both able to differentiate in vivo. In this study we examined the ability of these CD8+ thymocyte populations and of CD4−CD8− double‐negative thymocytes to change their phenotype during brief in vitro culture. CD8− thymocytes were prepared by anti‐CD4 plus complement lysis followed by positive selection of the survivors on anti‐CD8‐coated plates. After 16 h of culture, > 60% of CD8+ thymocytes became double‐positive. Both CD8hi and CD8lo cells were able to show this in vitro change: about 30% of the former and about 80% of the latter became double‐positive. In contrast to this, double‐negative thymocytes which had been depleted of cells expressing low densities of CD8 did not show such a phenotypic conversion in vitro. Further panning experiments suggested that all of the CD8+ thymocytes actually express a low surface density of the CD4 molecule which is undetectable in our cytofluorometric assays.
Longitudinal study of leukocyte functions in homosexual men seroconverted for HIV: rapid and persistent loss of B cell function after HIV infection
Authors: Terpstra Fokke G. , J. M. Al Bert , Roos Marijke T. H. L. , Wolf Frank De , Goudsmit Jaap , Schellekens Peter T. H. A. , Miedema Frank 
Published: March 2007

AbstractThe early effects of infection with human immunodeficiency virus (HIV) were investigated in homosexual men who had seroconverted for anti‐HIV antibodies. Leukocyte functional activities were determined in longitudinally collected peripheral blood mononuclear cell samples. During the first 10 months following seroconversion, anti‐CD3 monoclonal antibody‐induced T cell proliferation, monocyte accessory function and T helper activity on B cell differentiation in a pokeweed mitogen‐driven system were not affected. In contrast, from the moment of seroconversion on, B cells of seroconverted men failed to produce immunoglobulin in the pokeweed mitogendriven system. This defect was not restored by addition of normal CD4+ T cells. Immunoglobulin synthesis induced by Staphylococcus aureus and interleukin 2 decreased gradually, until it was completely lost 10 months after seroconversion. In addition, proliferation in response to anti‐IgM or Staphylococcus aureus by B cells from HIV seroconverted men was decreased. The lack of inducible in vitro B cell activity was not accompanied by elevated spontaneous Ig synthesis by B cells of the seroconverted men. In the second group of men studied during the 2nd year following seroconversion, T helper activity on normal B cell differentiation significantly decreased, whereas anti‐CD3‐induced T cell proliferation and monocyte accessory function were not significantly affected. Our results demonstrate that in almost all HIV‐infected individuals B cell functional defects are the first leukocyte abnormalities observed preceding defects in T helper activity.
The induction of protective immunity to Leishmania major in the BALB/c mouse by interleukin 4 treatment
Authors: Carter Katherine C. , Gallagher Grant , Baillie Alan J. , Alexander James 
Published: March 2007

AbstractThe ability of interleukin 4 (IL4), administered subcutaneously around the cutaneous lesion in the form of hydrophilic gels, to affect the development of established Leishmania major infections in the BALB/c mouse was studied. IL4 had a therapeutic effect on L. major lesion growth compared with control mice, causing not only resolution of the parasite lesions over a period of 10 weeks but also rendering animals resistant to reinfection. Adoptive transfer of splenic T cells, obtained from IL4‐treated animals, conferred significant resistance to L. major infection in naive BALB/c mice compared with controls. These results demonstrate that IL4 is capable of not only reversing the usual (i.e. non‐curing) course of L. major infection in the BALB/c mouse, but also of promoting the generation of protective immunity. The nature of the gel used to deliver the cytokine was found to be important since the therapeutic activity of IL4 in poloxamer gel was not observed when a hydroxypropylmethyl cellulose (hypromellose) gel was used as the IL4 vehicle.
The methylation state of the T cell antigen receptor β chain gene in subpopulations of mouse thymocytes
Authors: Sakamoto Shigeru , Mathieson Bonnie J. , Komschlies Kristin L. , Bhat Narayan K. , Young Howard A. 
Published: March 2007

AbstractPrevious analyses of T cell receptor β chain (TcR β) genomic DNA from subsets of human peripheral blood leukocytes suggested that the TcR β methylation pattern might reflect distinct differentiation pathways. The studies presented here, using murine thymocyte subsets, have specifically addressed the question of whether methylation of TcR β DNA is related to the cellular maturity and type of TcR β mRNA expressed in the different subsets. We have observed that the DNA isolated from either CD4+ or CD8+ thymocytes, the more mature thymic subsets, is less methylated in the TcR β region than DNA isolated from the CD4−CD8−, double‐negative population containing the more immature thymocytes. In addition, this pattern of DNA methylation is directly related to the ratio of 1.3‐kb to 1.0‐kb TcR β mRNA seen in these different cell types. Although a quantitative difference in the level of TcR β mRNA was noted for the two mature subsets, no qualitative difference in the ratio of 1.3‐kb to 1.0‐kb mRNA was detected. Furthermore, these DNA methylation patterns appear to be lineage related, because the TcR β region of genomic DNA isolated from mouse macrophages is heavily methylated.
Acceleration of the onset of diabetes in NOD mice by thymectomy at weaning
Authors: Dardenne Mireille , Lepault Françoise , Bendelac Albert , Bach Jean‐François 
Published: March 2007

AbstractThe effect of thymectomy performed at weaning (3 weeks) and at 6–7 weeks of age on the incidence of diabetes was examined in the non‐Obese diabetic (NOD) mouse, a spontaneous model of immunologically mediated insulin‐dependent diabetes similar to human type I diabetes. When performed at weaning, thymectomy led to a dramatic increase in the incidence of diabetes in NOD females in comparison to sham‐thymectomized animals. Conversely, no change in the incidence of the disease or the expression of insulitis was noted when thymectomy was performed in NOD males. When delayed beyond 6–7 weeks of age, thymectomy had no effect on NOD males and females. Flow cytometry analysis of spleen cells from intact mice and mice thymectomized at weaning or at 6–7 weeks of age demonstrated a significant depletion of the T cell subsets in both groups of thymectomized animals. These results indicate that the onset of diabetes in NOD mice is submitted to thymic regulation and that the T cell depletion induced by thymectomy at weaning accelerates the disease, an effect possibly due to the loss of some T cell‐dependent suppressor mechanisms.
Interleukin 5 is a differentiation factor for IgA B cells
Authors: Schoenbeck Simone , Mckenzie Douglas T. , Kagnoff Martin F. 
Published: March 2007

AbstractInterleukin 5 (IL 5) stimulates murine B cells to IgA production in vitro. The present study examined the B cell target of IL 5 activity, and asked whether IL 5 acts as an isotype switch factor, a growth factor, or a differentiation factor on B cells that produce the IgA isotype. Lipopolysaccharide‐activated surface IgM‐positive, surface IgA‐positive or surface IgA‐negative B cell populations from spleen or Peyer's patches were stimulated with IL 5, after which the expression of cell surface IgA, IgA secretion, and numbers of IgA‐secreting cells were determined. IL 5 increased the IgA response by acting on B cells that are already committed to IgA expression. Thus, with regard to the IgA response, IL 5 acts as a differentiation factor, rather than a growth or IgA isotype switch factor.
Pgp‐1hi T lymphocytes accumulate with age in mice and respond poorly to concanavalin A
Authors: Lerner Adam , Yamada Takatsugu , Miller Richard A. 
Published: March 2007

AbstractAging is associated with an accumulation of T cells functionally hyporesponsive to the effects of mitogens such as concanavalin A. Recent studies in mice and humans have identified surface markers useful for distinguishing antigen‐stimulated memory T cells from virgin T cells. In mice, memory T cells within the CD8+ cell population have been shown to express relatively high levels of the cell surface glycoprotein Pgp‐1. On the theory that aging might diminish the supply of virgin thymic emigrants without compromising the production of memory T cells, we examined the proportion of Pgp‐1hi CD4+ and CD8+ cells in the spleen, blood and lymph nodes of mice of varying age. We found a dramatic (2.5‐fold) age‐associated increase in the percentage of cells with the Pgp‐1hi phenotype. By limiting dilution methods, the frequency of concanavalin A‐responsive T cells was found to be significantly reduced in the Pgp‐1hi cell pool, whether measured by interleukin 2‐dependent proliferation, interleukin 2 production or generation of cytotoxic effectors. Pgp‐1hi and Pgp‐1lo T cells from young mice proliferate equally well when stimulated by optimal doses of phorbol myristate acetate and ionomycin suggesting that the poor responses to concanavalin A do not simply reflect low viability. Aging leads both to an increase in mitogen‐hyporesponsive Pgp‐1hi T cells, and also to lower responsiveness of cells in the Pgp‐1hi subset.
Molecular mapping of the human T cell receptor gamma (TRG) genes and linkage of the variable and constant regions
Authors: Lefranc Marie‐Paule , Chuchana Paul , Dariavach Piona , Nguyen Catherine , Huck Sylvie , Brockly Frédérique , Jordan Bertrand , Lefranc GÉRard 
Published: March 2007

AbstractIn the human T cell receptor gamma (TRG) locus, fourteen variable (TRGV) genes belonging to four subgroups have been identified upstream of two constant region (TRGC) genes. Three joining segments, JP1, JP and J1, have been localized upstream of TRGC1, and two others, JP2 and J2, upstream of TRGC2. In this report, we demonstrate that a unique Xho I fragment of 120 kilobases (kb) contains the fourteen TRGV genes and that the hybridization of that fragment in pulsed‐field gel electrophoresis (PFGE) allows linkage of the variable region to the constant region locus. We also show that the variable and the constant regions are remarkably close to each other since the distance between V11, the most 3′ V gamma gene, and JP1, the most 5′ J gamma segment, is only 16 kb. With its 14 V gamma genes, spanning 100 kb, the two C gamma genes and 5 joining segments covering less than 40 kb and only 16 kb separating the most 3′ V gene from the most 5′ J segment, the human TRG locus spans 160 kb of genomic DNA and represents a particularly condensed locus compared to the other rearranging gene loci.
Deletion of Mls‐reactive T cells in H‐2‐compatible but Mls‐incompatible bone marrow chimeras
Authors: Yoshikai Yasunobu , Ogimoto Masaro , Matsumoto Koji , Sakumoto Misao , Matsuzaki Goro , Nomoto Kikuo 
Published: March 2007

AbstractThe cellular basis of tolerance induction to Mls‐encoded antigens in radiation bone marrow (BM) chimeras has been investigated in two H‐2‐compatible strain combinations of AKR/J (H‐2k, Thy‐1.1, Mls‐Ia) and C3H/He (H‐2k, Thy‐1.2, Mls‐IIa). Sequential appearance of host‐ and donor‐derived T cell subsets and T cell receptor gene messages occurred in the peripheral lymphoid organs of both irradiated AKR/J mice reconstituted with C3H/He BM cells (C3H/He‐AKR/J chimera) and irradiated C3H/He mice reconstituted with AKR/J BM cells (AKR/J‐C3H/He chimera). A large number of cells expressing T cell receptor γ genes were detected in spleen on day 21 after reconstitution, while the normal level of alloreactivity was first detected in the spleen on day 56 after reconstitution in correlation with the appearance of appreciable levels of Thy‐1high cells and T cell receptor α and β gene transcripts. T cells bearing Vβ6, that is strongly correlated with reactivity to antigens encoded by the Mls‐Ia genetic locus, were virtually abolished in spleen on day 56 in both C3H/He‐AKR/J chimera and AKR/J‐C3H/He chimera. Furthermore, expression of Vβ3 gene transcripts, that are important for recognizing Mls‐IIa, was undetected either in the peripheral lymphoid cells of AKR/J‐C3H/He chimera or in those of C3H/He‐AKR/J chimera. These results suggested that clonal elimination of self‐reactive T cells bearing Vβ3 or Vβ6 was induced by both host‐derived radioresistant cells and donor‐derived repopulating cells in the thymus of radiation BM chimeras.