bluuebunny/crossref_metadata_2025_split huggingface dataset:
Membrane anchoring and spontaneous release of CD16 (FcR III) by natural killer cells and granulocytes
Authors: Lanier Lewis L. , Phillips Joseph H. , Testi Roberto 
Published: March 2007

AbstractCD16 is an IgG Fc receptor that is predominantly expressed on human natural killer (NK) cells and granulocytes. The CD16 antigen expressed on neutrophils is a 50 to 70‐kDa glycoprotein attached to the plasma membrane by a phosphatidylinositol‐glycan linkage that is susceptible to cleavage by phosphatidylinositol‐specific phospholipase C (PIPLC). By contrast, treatment of NK cells with PIPLC did not cleave CD16 from the cell surface. Biochemical analysis of the deglycosylated CD16 revealed a substantial difference in the core polypeptides expressed by NK cells and granulocytes. Culture of radiolabeled NK cells resulted in the spontaneous release of a CD16 molecule, smaller than the membrane form of CD16. These findings demonstrate that structural differences exist in the CD16 antigens expressed on NK cells and granulocytes that may potentially influence their functional activities.
Resistance of fetal PVG rats to induction of allograft tolerance
Authors: Mccullagh Peter 
Published: March 2007

AbstractArtificially induced immunological tolerance is often envisaged as experimental mimicry of events which occur naturally during the acquisition of self tolerance. Thus, it has been inferred that similar circumstances will facilitate the induction of both types of unresponsiveness. Since tolerance to most self determinants appears to have been established by the time of birth and allograft tolerance can be experimentally induced more readily, if not exclusively, in very young animals, it is commonly assumed that susceptibility to induction of tolerance to foreign antigens will continue to increase as progressively younger animals are tested. The experiments reported in this study extend the range of circumstances under which younger animals may be found to be less susceptible, or even completely resistant, to tolerance induction.While neonatal PVG rats were highly susceptible to the induction of tolerance to (PVG × DA)F1 hybrid determinants, fetal PVG rats were only partially susceptible at 19 days and were completely resistant at 17 and 18 days of gestation. Furthermore, only 39% of neonatal PVG rats that had been inoculated with F1 hybrid bone marrow cells at 18 days of gestation could be rendered tolerant by procedures which were effective in 100% of previously untreated neonates. These observations were interpreted to indicate that a certain stage of maturity must be attained before fetal rats become susceptible to tolerance induction.Asymmetry in susceptibility to tolerance induction in response to the inoculation of F1 hybrid bone marrow cells was observed when PVG and DA fetuses, but not neonates, were compared. This difference in the response of the two strains recalls the divergence in immune reactivity of offspring, previously reported when PVG and DA embryos were transferred to surrogate mothers of the other strain. It is also in agreement with earlier reports of substantial differences in the ease of tolerance induction between different strain combinations. The asymmetry between PVG and DA rats in the present experiments is speculatively attributed to differences in rates of immunological maturation of the two strains.
Enhanced responsiveness of human memory T cells to CD2 and CD3 receptor‐mediated activation
Authors: Sanders Martin E. , Makgoba Malegapuru W. , June Carl H. , Young Howard A. , Shaw Stephen 
Published: March 2007

AbstractPrevious investigations have defined phenotypic differences between unprimed (naive) and antigen‐primed (memory) T cells from human peripheral blood. We now report that memory T cells proliferate much more than naive cells when stimulated with anti‐CD3 monoclonal antibody or pairs of anti‐CD2 monoclonal antibodies. Enhanced responsiveness to receptor‐mediated triggering is a novel mechanism for T cells which could facilitate memory cell response to specific antigen. Furthermore, when triggered via either CD2 or CD3, memory T cells produce substantial amounts of interferon gamma while naive cells produce virtually none; this suggests that differentiation from naive to memory state is accompanied by a stable change in regulation of the gene for interferon‐γ. We conclude that naive and memory T cells are dramatically different in function as well as phenotype.
Expression and function of AIM, an activation inducer molecule of human lymphocytes, is dependent on the activation of protein kinase C
Authors: Cebrián Marta , Redondo Juan Miguel , López‐Rivas Abelardo , Rodríguez‐Tarduchy Gemma , De Landázuri Manuel O. , Sánchez‐Madrid Francisco 
Published: March 2007

AbstractAIM is an activation inducer molecule selectively expressed by activated lymphocytes through which agonistic proliferative signals can be triggered. The relationship between the expression of AIM with the activation of protein kinase C (PKC) has been studied. Different activators of PKC such as the active phorbol esters, phorbol myristate acetate and phorbol dibutyrate, or the phorbol‐related ester mezerein were able to induce AIM expression on peripheral blood lymphocytes as assessed by immunofluorescence flow cytometry. Moreover, the expression of this activation antigen was also induced by treatment of peripheral blood lymphocytes either with dioctanoyl‐rac‐glycerol, a synthetic analogue of diacylglycerol, the physiological mediator of PKC activation. Further indirect evidence that AIM expression was dependent on the activation of PKC was obtained by blockade of the induction of its expression in cells treated with H7, an inhibitor of PKC. The AIM expression can be detected as early as 3 h after addition of phorbol esters and it requires active RNA and protein synthesis. The activation of PKC appears to be also required in the proliferative response induced by anti‐AIM monoclonal antibody (mAb) in conjunction with phorbol esters. Agents such as phorbol myristate acetate, phorbol dibutyrate or mezerein but not the inactive phorbol ester methyl‐phorbol myristate acetate induced a high proliferation of peripheral blood lymphocytes in the presence of anti‐AIM mAb. In addition, we have demonstrated that the anti‐AIM mAb is not sufficient by itself to induce cellular proliferation once the AIM antigen is expressed at the cell surface, requiring the simultaneous stimulation of the PKC to trigger high proliferative responses. Furthermore, the anti‐AIM mAb did not appear to exert its effect on proliferation by rapidly increasing the intracytoplasmic Ca2+ levels. Taken together all these results indicate that the expression and function of AIM antigen is dependent on the activation of PKC.
Dual role of macrophages in the suppression of interleukin 2 production and interleukin 2 receptor expression in trypanosome‐infected mice
Authors: Sileghem Maarten , Darji Ayub , Hamers Raymond , Winkel Marnix Van De , Baetselier Patrick De 
Published: March 2007

AbstractLymph node cells derived from T. brucei‐infected mice fail to produce interleukin 2 (IL 2) subsequent to a potent mitogenic trigger and actively suppress the capacity of normal cells to produce IL 2 in co‐culture experiments. The depletion of Thy‐1+ cells does not decrease but rather increases the suppressive potential of the LNC derived from infected mice. A T cell‐enriched nylon wool‐nonadherent fraction, on the other hand, is not suppressive. The suppression of IL 2 production is promptly restored by the addition of prostaglandin synthesis inhibitors suggesting a key role of the prostaglandin‐producing macrophages. Our data indicate that such macrophages do not act indirectly through the induction of suppressor T cells, but rather directly interfere with the normal lymph node cells.In contrast to the essential role of prostaglandins in the impairment of IL 2 production, these mediators are not involved in the suppression of IL 2 receptor expression. Lymph node cells derived from Trypanosoma brucei‐infected mice fail to produce interleukin 2 (IL 2) subsequent to a potent mitogenic trigger and actively suppress the capacity of normal cells to produce IL 2 in co‐culture experiments. The depletion of Thy‐1+ cells does not decrease but rather increases the suppressive potential of the LNC derived from infected mice. A T cell‐enriched nylon wool‐nonadherent fraction, on the other hand, is not suppressive. The suppression of IL 2 production is promptly restored by the addition of prostaglandin synthesis inhibitors suggesting a key role of the prostaglandin‐producing macrophages. Our data indicate that such macrophages do not act indirectly through the induction of suppressor T cells, but rather interfere directly with the normal lymph node cells.
Developmentally regulated expression of the neural cell adhesion molecule (NCAM) by mouse thymocytes
Authors: Brunet Jean‐François , Hirsch Marie‐Rose , Naquet Philippe , Überla Klaus , Diamantstein Tibor , Lipinski Marc , Goridis Christo 
Published: March 2007

AbstractThe expression of the neural cell adhesion molecule (NCAM) has been investigated during thymus ontogeny. NCAM mRNA was readily detectable at day 19 of gestation, the youngest age studied. Its level declined after birth to become undetectable at 3 weeks of age. Cell surface expression of NCAM protein was detected on 14% of day 15 fetal thymocytes and peaked during the perinatal period, when around 40% of the thymocytes expressed low to medium levels of NCAM. At postnatal day 2, the vast majority of the NCAM+ cells were also CD4+ and CD8+. At embryonic day 15, NCAM appeared also to be expressed by CD4− thymocytes since 14% of the cells were already NCAM+ whereas CD4 was virtually undetectable. In frozen section of the newborn thymus, surface staining for NCAM was present on a subpopulation of cells in the cortex, rare in the medulla and absent from the sub‐capsular area. In conjunction with other cell adhesion molecules, NCAM could play a role in cell interactions during thymic development.
Translation affects immunoglobulin mRNA stability
Authors: Jäck Hans‐Martin , Berg Jörg , Wabl Matthias 
Published: March 2007

AbstractWhen termination codons were introduced into exons of the gene for Ig m̈ chain, steady‐state levels of m̈ mRNA were reduced, both at the pre‐B cell stage and at the plasma cell stage. A termination codon in the variable region gene segment and a termination codon in the second exon of the constant region gene segment had effects of similar magnitude. When the termination codon was deleted, the original level of mRNA was restored. The rate of m̈ gene transcription was the same whether or not a termination codon was present. Therefore, the termination codons must reduce the amount of the mRNA by reducing its stability. Since the introduced termination codons prematurely terminate translation and, in so doing, change the ribosome load on the mRNA, we conclude that m̈ mRNA stability is conferred in part by ribosomal protection from enzymatic degradation. We propose that the differences in m̈ mRNA stability during B lymphocyte differentiation are due to different amounts of ribosomes available for translation.
The effects of anti‐CD2 antibodies on the differentiation of mouse thymocytes
Authors: Kyewski Bruno A. , Jenkinson Eric J. , Kingston Rosetta , Altevogt Peter , Owen Michael J. , Owen John J. T. 
Published: March 2007

AbstractUsing a rat monoclonal antibody against mouse CD2, we determined the expression of this marker on thymocytes during ontogeny. CD2 expression becomes detectable at day 15 and reaches adult levels (∼95% positivity) by day 19. Furthermore, the effect of anti‐CD2 antibodies on T cell differentiation was analyzed by addition of antibodies to thymus organ cultures or repeated injection into newborn mice. Anti‐CD2 antibodies inhibit CD2 expression in organ cultures and drastically reduce its expression on thymocytes and peripheral lymphocytes in vivo. In either situation, suppression of CD2 expression does not significantly alter the generation of T cells expressing CD3, CD4, CD8 and T cell receptor Vβ8. These results do not support a role for CD2 in early steps of thymocyte differentiation.
E‐series prostaglandins are potent growth inhibitors for some B lymphomas
Authors: Phipps Richard P. , Lee David , Schad Victoria , Warner Garvin L. 
Published: March 2007

AbstractThe ability of prostaglandins (PG) to inhibit the growth of B cell lymphomas was investigated. Macrophage‐secreted PGE2 was previously shown to promote unresponsiveness to antigen in normal B lymphocytes. This observation suggested that B lymphomas might also be regulated by prostanoids. Five non‐PG‐secreting Ly‐1+ B lymphomas (CH12, CH31, CH33, NBL and WEHI‐231) were incubated for 24–72 h with PGE2, PGE1 or PGF2 α. The level of lymphoma growth at the end of culture was determined using a colorimetric assay which detects only viable cells. A marked heterogeneity was observed with respect to the sensitivity of these lymphomas to PGE2 and PGE1. CH31 was very sensitive, being growth inhibited by as little as 10−8 M PGE. In contrast, CH12, a more mature lymphoma, was highly resistant, whereas CH33, NBL and WEHI‐231 were of intermediate resistance. All five lymphomas demonstrated little or no growth inhibition when cultured with PGF2 α. Moreover, unlike PGE2, PGF2 α failed to elevate intracellular cAMP levels. It was previously shown that CH31, CH33 and WEHI‐231 could be growth inhibited by anti‐immunoglobulin antibodies which cross‐link surface immunoglobulin. Interestingly, these three lymphomas were rendered more sensitive to this treatment if PGE2 was present. For example, 10−8 M PGE2 alone had little effect on CH33, but significantly augmented growth inhibition induced by suboptimal quantities of anti‐immunoglobulin antibody. Cholera toxin, another agent which was found to rapidly elevate intracellular cAMP levels, also synergized with suboptimal doses of anti‐immunoglobulin to induce growth inhibition. Overall these data suggest that, in vivo, macrophage‐secreted prostanoids may slow the growth of some lymphomas and that anti‐immunoglobulin or anti‐idiotype treatment may be more effective in the presence of agents which elevate cAMP such as E‐series PG.
Mapping of murine IgE epitopes involved in IgE‐Fcε receptor interactions
Authors: Schwarzbaum Shelley , Nissim Ahuva , Alkalay Irit , Ghozi Mireille C. , Schindler Daniel G. , Bergman Yehudit , Eshhar Zelig 
Published: March 2007

AbstractThe generation of anti‐IgE monoclonal antibodies has permitted the identification of various serological epitopes on the IgE molecule. The relationship of the sites on IgE recognized by such antibodies to the Fc epsilon receptor (FcER) interaction site has been determined using cross‐inhibition studies. However, interpretation of this type of experiment is limited by problems of steric hindrance. Thus, to accomplish precise mapping on the IgE molecule of the FcεR interaction site and the binding sites of various anti‐IgE mAb, we employed site‐directed mutagenesis of the IgE heavy chain gene.To this end we have constructed and expressed a recombinant murine constant E heavy chain (Cε) gene bearing a (4‐hydroxy‐3‐nitrophenyl)acetic acid (NP)‐binding VH region. Several site‐specific mutants in the Cε3 and Cε4 domains of this recombinant Cε gene were prepared and expressed by transfection into the light chain‐producing J558L myeloma cell line. The resulting IgE antibodies were tested for binding to mast cells and to various anti‐IgE mAb.The mutants produced include a proline to histidine point mutant at amino acid residue 404 in the Cε3 domain, a mutant with a truncated Cε4 domain, a mutant with a 45 amino acid deletion in the carboxy end of Cε3, and a chimeric human Cε in which the human Cε3 was replaced by the homologous mouse Cε3 domain. These mutants have permitted the localization, to the Cε3 domain, of the epitopes recognized by the 84.1C and 95.3 anti‐IgE mAb. The 84.1C mAb recognizes a site on IgE which is identical or very close to the FcεR binding site, and 95.3 recognizes a site on IgE which is related, but not identical to the FcεR binding site. The antigenic determinant recognized by the 51.3 mAb, which is inefficient at blocking the IgE‐FcεR interaction, has been mapped to the Cε4 domain. When tested for binding to the FcεR on RBL‐2H3 cells, the point mutant bound to the FcεR with twofold reduced affinity, while the Cε3 deletion mutant and the mutant truncated in Cε4 lost all receptor binding activity. These data suggest that the FcεR binding site can be assigned to the third C region domain, and that the fourth domain, while not directly involved in FcεR binding, may play a role in the formation of the H2L2 tetrameric IgE molecule, and in stabilizing the conformation of IgE required for FcεR binding.
Cultured keratinocyte grafts are recognized, but not rejected by CD8+ T cells in vivo
Authors: Tinois Estelle , Cobbold Steve , Faure Michel , Yeoman Helen , Stanley Margaret 
Published: March 2007

AbstractIt has been shown in the mouse that cultured keratinocyte allografts [fully major histocompatibility complex (MHC) mismatched] survive for at least 100 days without evidence of rejection. In an attempt to analyze the immune mechanisms underlying this phenomenon we have investigated the induction of tolerance to such grafts. Primary cultures of BALB/c keratinocytes were prepared using irradiated 3T3 feeder cells, and the cultured cell sheets were grafted, using a silicone transplantation chamber, onto CBA recipients. After the cultured grafts had been in place for 4–6 weeks full‐thickness tail skin from BALB/c donors was grafted onto the dorsal flank opposite the cultured graft. The median graft survival time of these full‐thickness allografts was 15.5 days compared to 13 days in the control group.These data show that in the absence of Langerhans cells and MHC class II expression, keratinocytes expressing class I and minor histocompatibility antigens induce a prolonged survival of full‐thickness skin allografts. The results from experiments in which T cell subsets were depleted in vivo suggest that CD8+ cells (a) recognize the class I alloantigens of the cultured graft, (b) do not reject the cultured graft and (c) do not progress further in their maturation pathway. We propose that these CD8+ T cells might have been partially primed by receiving only the first signal of activation and that they may be equivalent to ‘poised’ cytotoxic T cells. These CD8+ cells can reject non cultured full‐thickness skin grafts, and do so more effectively after removing CD4+ cells.
Cytokine mRNA levels in antigen‐stimulated peripheral blood mononuclear cells
Authors: Gauchat Jean‐François , Gauchat Dominique , De Weck Alain L. , Stadler Beda M. 
Published: March 2007

AbstractLevels of cytokine mRNA coding for granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), interferon‐γ (IFN‐γ), interleukin (IL) 2, IL 1β, IL 4 or IL 6 have been measured by Northern blot analysis after antigen stimulation. As source for RNA we used peripheral blood mononuclear cells (PBMC) from donors which showed a proliferative response after tetanus toxoid or Candida albicans stimulation. For comparison PBMC were also stimulated with lectins and anti‐CD3 antibody. With some variations among donors, antigens clearly induced measurable levels of IFN‐γ, GM‐CSF and IL 2 mRNA. Increased levels for IL 6 were also detected after antigen stimulation. In contrast to polyclonal T cell stimuli, antigens showed delayed kinetics of mRNA steady‐state levels and resembled in this respect more closely the stimulation with pokeweed mitogen. Thus, cytokine mRNA levels may be assessed in unfractioned PBMC after antigen stimulation. The two tested antigens also clearly show a cytokine pattern distinct from that induced in polyclonal stimulations such as anti‐CD3.
Two monoclonal antibodies specific for the T cell receptor Vα8
Authors: Tomonari Kyuhei , Lovering Erin , Fairchild Sue , Spencer Sarah 
Published: March 2007

AbstractTwo monoclonal antibodies, KT50 and KT65, specific for Vα8 have been established. This was determined as follows: (a) 4 T cell clones, C6, R1, G22 and 19, out of 43 T cell clones with various antigen specificities, major histocompatibility complex restrictions and Vβ usages not only bound KT50 and KT65 but also expressed Vα8 mRNA, (b) KT50 and KT65 precipitated molecules from the clone C6 similar to the T cell receptor molecules precipitated in C6 cells by KT11 (anti‐Vβ11) or KTL2 (anti‐Ti) and (c) KT50 and KT65 were mitogenic and induced cytotoxicity. All strains of mice so far examined have populations of KT50+ and KT65+ T cells of 1.4%−3.6% and 0.9%−2.6%, respectively. Different H‐2 haplotypes were not observed to affect the number of cells expressing KT50 or KT65. In addition KT15 (anti‐CD8), without cross‐linking to KT50 or KT65, augmented proliferation triggered by KT50 or KT65.
Effect of cyclosporin A on T cell immunity II. Defective thymic education of CD4 T helper cell function in cyclosporin A‐treated mice
Authors: Fukuzawa Masahiro , Sharrow Susan O. , Shearer Gene M. 
Published: March 2007

AbstractCyclosporin A (CsA) is an immunosuppressive agent that is widely used in transplantation. Recent animal studies indicate that CsA can affect the development of immunity so that autoreactive T lymphocytes are generated. In this study, mice were treated with CsA prior to irradiation and transplantation of syngeneic bone marrow to determine whether CsA pretreatment would affect the ability of the bone marrow recipients to develop normal T cell function. Our results indicate that (a) thymuses of CsA‐treated mice do not contain single‐positive thymocytes (i.e. L3T4+Ly‐2− or L3T4−Ly‐2+) during i.p. treatment with 15 mg/kg/day of CsA; (b) both populations of single‐positive thymocytes reappear within 2 weeks of termination of CsA and (c) irradiation and bone marrow reconstitution of these CsA‐treated mice results in reconstitution of normal numbers of L3T4+ and Ly‐2+ cells, but the L3T4+ T cells to not provide T helper function, as determined by interleukin 2 production and cytotoxic T lymphocytes generation. These findings indicate that CsA can affect thymic microenvironment and may be important as a model for investigating intrathymic T cell maturation. Our results may also have clinical implications for T lymphocyte development in transplant patients receiving CsA.
Alloreactive cytotoxic T cells induce DNA fragmentation in peritoneal macrophages: evidence for target cell killing by cytotoxic T cells in vivo
Authors: Liu Yang , Waring Paul , Müllbacher Arno 
Published: March 2007

AbstractThis report addresses the question whether cytotoxic T cells can cause target cell death in vivo by examining target cell DNA fragmentation. The results show that alloreactive cytotoxic T cells induced significant DNA fragmentation in peritoneal macrophages in vivo and that the DNA fragment was a multiple of 180 ± 30 bp. Furthermore, the effector cells which caused this characteristic DNA fragmentation were CD8+ T cells. These results demonstrate that cytotoxic T cells can cause target cell death in vivo.