bluuebunny/crossref_metadata_2025_split huggingface dataset:
High frequency of CD8αα homodimer‐bearing T cells in human fetal intestine
Authors: Latthe Manish , Terry Linda , Macdonald Thomas T. 
Published: March 2007

AbstractImmunohistochemistry on frozen sections was used to identify CD8αα cells and CD8αβ cells in human intestine. As observed previously, CD8αβ cells predominate (>95%) in tonsil and post‐natal intestine. However in human fetal intestine (16–24 weeks gestation), almost half the CD8+ cells in the lamina propria are CD8αα, and many CD8αα cells can be identified in the epithelium. In contrast, in the T cell zones of the Peyer's patches, CD8αβ cells are dominant. The CD8αα cells are virtually all αβ T cell receptor positive. By analogy with the murine system, these CD8αα cells in the fetal gut may be directly derived from the marrow, undergoing thymus‐independent differentiation in the gut mucosa.
Delayed allograft rejection by T cell receptor Vβ8.1 transgenic mice peripherally tolerized to Mls‐1
Authors: Bhandoola Avinash , Bassiri Hamid , Markmann James F. , Yui Katsuyuki , Hashimoto Yasuhiro , Greene Mark I. 
Published: March 2007

AbstractOne commonly studied model system for peripheral tolerance is the antigen‐specific unresponsiveness of T cells from mice previously inoculated with superantigens such as Mls‐1a. In this study, we used a TcR Vβ8.1 transgenic mouse model to investigate whether mice peripherally tolerized to Mls‐1a exhibit delayed skin allograft rejection. We report dramatic prolongation of skin allograft survival in Vβ8.1 transgenic but not in non‐transgenic mice tolerized to Mls‐1a. Peripherally induced unresponsiveness to Mls‐1a can, therefore, be considered true tolerance.
Lack of association of Vβ8+ T cells with lupus‐like syndrome in MRL‐lpr/lpr mice
Authors: Fossati Liliane , Merino Ramón , Iwamoto Masahiro , Lemoine Robert , Izui Shozo 
Published: March 2007

AbstractTo evaluate the role of Vβ8+ T cells in the development of lupus‐like autoimmune syndrome in MRL‐lpr/lpr mice, we treated them with the F23.1 anti‐Vβ8 monoclonal antibody (mAb) from birth to 4 months of age. Here we report that almost complete depletion of Vβ8+ T cells by the F23.1 mAb treatment neither inhibited nor delayed the development of hypergammaglobulinemia, autoantibody production and autoimmune glomerulonephritis in MRL‐lpr/lpr mice. In addition, the F23.1 mAb treatment did not prevent the development of lymphadenopathy and the generation of a CD4−CD8− double‐negative T cell subset, characteristically accumulating in lpr lymph nodes. Our results strongly argue against the idea that the Vβ8+ T cells play a critical role in the development of lupus‐like autoimmune syndrome in MRL‐lpr/lpr mice.
T cells which do not express membrane tumor necrosis factor‐α activate macrophage effector function by cell contact‐dependent signaling of macrophage tumor necrosis factor‐α production
Authors: Suttles Jill , Milleru Robert W. , Taou Xiang , Stoutf Robert D. 
Published: March 2007

AbstractPrevious studies have suggested that T cell contact‐dependent signaling of macrophages (MΦ) is mediated by membrane tumor necrosis factor‐α (memTNF‐α), based on the observation that anti‐TNF‐α could inhibit T cell‐mediated MΦ activation. The current report confirms that anti‐TNF‐α does inhibit activation of interferon‐γ (IFN‐γ)‐primed MΦ by paraformaldehyde‐fixed activated T cells. However, the involvement of membrane molecules other than memTNF‐α in the contact‐dependent signaling is suggested by two lines of evidence. First, the TH2 clone, AK8, displayed neither secreted TNF‐α/β nor memTNF‐α/β detectable by bioassay or immunofluorescence. Nonetheless, AK8 cells were equally effective, on a per cell basis, in contact‐dependent signaling of MΦ activation as TH2 and TH1 cells which do express memTNF‐α. Second, the expression of memTNF‐α by the TH clone, D10.G4, is maximal 24 h after activation, whereas the ability of this clone to activate MΦ is maximal at 6–8 h of activation and declines thereafter. Since TNF‐α is known to play a critical role in activation of MΦ effector function, it was hypothesized that T cell membrane components other than memTNF‐α might signal MΦ production of TNF‐α, thus allowing autocrine TNF‐α stimulation of MΦ effector function. In support of this, it is demonstrated that paraformaldehyde‐fixed activated TH2 cells can induce de novo production and release of TNF‐α by MΦ. This effect was not an artifactual result of paraformaldehyde fixation since paraformaldehyde‐fixed resting T cells did not induce TNF‐α gene expression. Previous studies have demonstrated a role for autocrine TNF‐α stimulation in LPS induction of effector function in recombinant IFN‐γ‐primed MΦ. The current study confirms that TNF‐α plays a critical role in T cell contact‐dependent signaling of MΦ but indicates that memTNF on the T cells may not be a sine qua non factor for contact‐dependent signaling. The data suggest that other T cell membrane molecules contribute to activation of MΦ effector function by stimulation of MΦ TNF‐α production.
Dose‐dependent T cell tolerance to an immunodominant self peptide
Authors: Cabaniolsu Jean‐Pierre , Cibottiu Ricardo , Kourilskyu Philippe , Kosmatopoulosu Konstandinos , Kanellopoulos Jean M. 
Published: March 2007

AbstractWe have previously described a model of tolerance to self peptides in a mouse transgenic (Tg) line producing secreted hen egg‐white lysozyme (HEL). The HEL cDNA was placed under the control of a ubiquitous promoter expressed early in embryogenesis, so that HEL should be present in Tg mice throughout the development of the immune system. Since individual HEL Tg mice express different amounts of serum HEL, we were previously able to show that H‐2d mice with HEL blood level > 10 ng/ml are tolerant to HEL and to the immunodominant (ID) peptide 108–116. However, autoreactive T lymphocytes recognizing the HEL subdominant (SD) peptides 74–96 and 1–18 still persist and the SD‐specific responses disappear at higher blood HEL concentrations. In the present work, we have studied HEL Tg H‐2d mice with HEL serum levels < 10 ng/ml (HEL‐low Tg animals). We find that 50% of Tg animals with HEL blood concentration < 2 ng/ml are responsive to HEL in T cell proliferation assays, although these responses are lower than those seen in non‐Tg control mice. The HEL‐specific T lymphocytes react only with 15‐mer overlapping peptides encompassing the single H‐2d ID region of HEL (residues 102–122); whereas the 9‐mer minimal ID peptide 108–116, which strongly triggers non‐Tg T cells, is unable to stimulate auto‐reactive T cells in vitro from HEL‐low Tg mice. Altogether, our results suggest that T lymphocytes specific for the minimal ID peptide are deleted or inactivated, while T cell clones of lower affinity and reacting with epitopes on longer peptides persist. Thus, the high affinity ID peptide‐specific T cell clones can be negatively selected even in the presence of low amounts of HEL.
Progenies of fetal thymocytes are the major source of CD4−CD8+ αα intestinal intraepithelial lymphocytes early in ontogeny
Authors: Lin Tesu , Matsuzaki Goro , Kenai Hiroyuki , Nomoto Kikuo 
Published: March 2007

AbstractPresent literature supports the view of an extrathymic origin for the subset of intestinal intraepithelial lymphocytes (IEL) that express the CD4−CD8+ αα phenotype. This subset would include virtually all T cell receptor (TCR) γδ IEL and a portion of TCR αβ IEL. However, these reports do not exclude the possibility that some CD4−CD8+ αα IEL are actually thymically derived. To clarify this issue, we examined the IEL day 3 neonatally thymectomized (NTX) mice. NTX resulted in as much as 80 % reduction in total TCR γδ IEL and in a nearly complete elimination of TCR αβ CD4−CD8+ αα IEL early in ontogeny (3‐to 5‐week‐old mice). The thymus dependency of TCR γδ IEL and TCR αβ CD4−CD8+ IEL was less prominent in older mice (7‐ to 10‐week‐old mice), as the total number of these IEL increased in NTX mice, but still remained severalfold less than that in euthymic mice. Furthermore, we demonstrate, by grafting the fetal thymus of CBF1 (H‐2b/d) mice under the kidney capsule of congenitally nude athymic mice of BALB/c background (H‐2d), that a substantial number of TCR γδ IEL and TCR αβ CD4−CD8+ αα IEL can be thymically derived (H‐2b+). In contrast, but consistent with our NTX data, grafting of adult thymi into nude mice generated virtually no TCR γδ IEL and relatively less TCR αβ CD4−CD8+ αα IEL than did the grafting of fetal thymi. These results suggest that the thymus is the major source of TCR γδ and TCR αβ CD4−CD8+ αα IEL early in ontogeny, but that the extrathymic pathway is probably the major source of these IEL later in ontogeny. A reassessment of the theory that most CD4−CD8+ IEL are extrathymically derived is needed.
Cytokine synthesis analyzed at the single‐cell level before and after revaccination with tetanus toxoid
Authors: Fernandez Victor , Anderssonu Jan , Anderssonu Ulf , Troye‐Blombergf Marita 
Published: March 2007

AbstractTetanus toxoid (TT) is a potent immunogen which evokes strong antibody responses after immunization. Here, TT was used as a model antigen to study the production of cytokines at the single‐cell level during the in vitro immune response to a specific recall antigen. Peripheral blood mononuclear cells were obtained from healthy volunteers before and 9 weeks after TT vaccination and were cultured with antigen in vitro. The kinetics of cytokine synthesis as well as frequencies of cytokine‐producing cells were determined at the single‐cell level by immunofluorescent intracellular staining of the cytokine protein. The phenotype of the producer cells was revealed by concomitant staining of surface markers.Two patterns of cytokine synthesis were induced by TT: (i) T lymphocytes expressed a number of lymphokines (interleukin (IL)‐2, IL‐3, IL‐4, IL‐10, interferon (IFN)‐γ and tumor necrosis factor (TNF)‐β), each with distinct kinetics of synthesis. This cytokine expression was strictly dependent on the previous exposure of the donor to TT and positively correlated with the level of tetanus immunity, as judged by TT‐specific Ab levels in plasma as well as lymphoproliferation. Cells producing IL‐2, IFN‐γ and particularly TNF‐β dominated this in vitro response. After 96–120 h in culture, 1.0–1.3% of the cells produced TNF‐β, i.e. frequencies at least tenfold higher than for any of the other lymphokines assayed. The addition of IL‐2 to the cultures caused a fourfold increase and a kinetics shift in the production of TNF‐β, which peaked already at 24 h. Exogenously added IL‐2 also caused a five‐ to tenfold increase in the number of IL‐2 and IFN‐γ producers but no apparent change in the kinetics of intracellular lymphokine appearance. (ii) The cytokines IL‐1α, IL‐1β, IL‐6 and TNF‐α were produced by monocytes. This inflammatory monokine response was independent of the TT‐specific immune status of the donors, characterized by a rapid onset and was transient.
Human RANTES induces the migration of human T lymphocytes into the peripheral tissues of mice with severe combined immune deficiency
Authors: Murphy William J. , Taubu Dennis D. , Anveru Miriam , Conlonu Kevin , Oppenheimu Joost J. , Kelvinu David J. , Longof Dan L. 
Published: March 2007

AbstractThe human cytokine, Recombinant Human Regulated on Activation, Normal T Expressed and Secreted (rhRANTES), is a small glycoprotein secreted by activated T cells and platelets and is structurally related to a family of chemotactic cytokines called chemokines. Evaluation of the effects of chemokines on human cells has largely been limited to in vitro binding assays. In an effort to study the in vivo effects of chemokines on human leukocyte migration, we examined the ability of rhRANTES to induce human T cell infiltration using a human/severe combined immune deficient (SCID) mouse model. SCID mice received human peripheral blood lymphocytes, followed by sequential subcutaneous injections of rhRANTES in the hind flank for 3 days. The skin and underlying tissue from the rhRANTES injection site were then biopsied and examined for the extent of human mononuclear cell infiltration. rhRANTES induced significant mononuclear cell accumulation 72 h after injection. Immunohistological evaluation determined that the majority of the cells recruited in response to rhRANTES injections were human CD33+ T cells with equal numbers of CD4+ and CD8+ cells. In contrast, subcutaneous injections of recombinant human macrophage colony‐stimulating factors resulted in little human cellular infiltration. Murine mononuclear cell infiltration in response to rhRANTES was also present suggesting that the in vivo effects of rhRANTES may be both direct and indirect. These results demonstrate that rhRANTES induces significant human T cell migration in vivo and suggests that the human/SCID mouse model may provide an important tool in studying the in vivo effects of chemokines on human leukocytes and leukocyte subsets.
Soluble CD23 potentiates interleukin‐1‐induced secretion of interleukin‐6 and interleukin‐1 receptor antagonist by human monocytes
Authors: Herbelin André , Elhadadu Sonia , Ouaazu Fateh , de Grooteu Donat , Descamps‐Latschaf Béatrice 
Published: March 2007

AbstractThe low‐affinity receptor for IgE (CD23) is cleaved into biologically active soluble fragments (sCD23), some of which have been reported to exhibit pleiotropic activities. However, it is not known whether the sCD23 fragments contribute to the induction and/or regulation of pro‐inflammatory cytokine production. In this study, this possibility was tested using interleukin (IL)‐1‐stimulated human whole blood as an ex vivo model of cytokine cascade production. We show that human recombinant 25‐kDa sCD23 significantly enhanced the production of IL‐6 in whole blood stimulated by IL‐1, but had only little or no effect in the absence of IL‐1. The potentiating effect of sCD23 was concentration dependent within the range of plasma levels occurring during various inflammatory processes in man. These results prompted us to study whether sCD23 and IL‐1 together also enhance the production of regulating factors exhibiting anti‐cytokine activities. Our data indicate that sCD23 augments the release of IL‐1 receptor antagonist induced by IL‐1. Finally, examining the effect of sCD23 on human peripheral monocytes stimulated by IL‐1, we confirmed the capacity of sCD23 to potentiate cytokine production. We suggest that sCD23 can modulate monocyte functions, thereby contributing to the amplification and regulation of immune and inflammatory processes.
Clonal expansions of Vδ1+ and Vδ2+ cells increase with age and limit the repertoire of human γδ T cells
Authors: Giachino Claudia , Granzierou Luisa , Modenau Vittorio , Maioccou Vincenzo , Lomateru Claudia , Fantiniu Flavio , Lanzavecchia Antonio , Migonef Nicola 
Published: March 2007

AbstractWe have investigated the complexity of the human γδ T cell repertoire by means of a VJ heteroduplex analysis method. cDNA obtained from peripheral blood mononuclear cells was amplified with Vδ1‐Cδ or Vδ2‐Cδ primers. The product was denatured and renatured to allow random reannealing of the strands and the heteroduplexes carrying mismatched junctional sequences were separated from the homoduplexes on polyacrylamide gels. Whenever one or more T cell clones were expanded to over 10% of the polyclonal background, discrete bands of homo‐ and heteroduplex appeared.This method was applied to the analysis of the peripheral γδ compartment from healthy donors and rheumatoid arthritis patients of different ages. While samples from young individuals showed a polyclonal pattern, a clear tendency towards oligoclonality appeared with increasing age, both in normal individuals and rheumatoid arthritis patients. We also show that the VJ junctional sequence derived from the heteroduplex fragments can be successfully used to isolate and characterize the corresponding T cell clones in vitro, even after a period of 1 year. In conclusion, our findings indicate that the complexity of the γδ T cell repertoire decreases with age as a consequence of the expansion of a few T cell clones.
Decreased expression of the ligand for CD40 in newborn lymphocytes
Authors: Fuleihan Ramsay , Ahern Deborah , Geha Raif S. 
Published: March 2007

AbstractImmune responses in newborn lymphocytes show a defect in isotype switching from IgM to IgG and IgA. Immunoglobulin isotype switching in B lymphocytes requires a contact‐dependent signal from T lymphocytes which is delivered by the ligand for the B cell surface antigen CD40. We investigated the capacity of newborn lymphocytes to express the CD40 ligand and to undergo CD40 ligand‐dependent immunoglobulin isotype switching. After stimulation by phorbol ester and ionomycin, newborn lymphocytes expressed markedly decreased amounts of CD40 ligand on their surface compared to normal adult lymphocytes. Northern blot analysis of mRNA derived from activated cord blood lymphocytes also revealed markedly decreased amounts of CD40 ligand mRNA. Decreased expression of CD40 ligand in newborn lymphocytes was associated with a severely decreased ability to undergo T cell‐dependent immunoglobulin isotype switching. Newborn lymphocytes synthesized little or no detectable IgE in response to T cell‐dependent stimulation by interleukin‐4 but synthesized IgE in response to T cell‐independent stimulation by CD40 monoclonal antibody and interleukin‐4. These results indicate that decreased expression of CD40 ligand in newborn lymphocytes may be the underlying cause of deficient immunoglobulin isotype switching in newborns.
Nitric oxide synthase: MRNA expression of different isoforms in human monocytes/macrophages
Authors: Reiling Norbert , Ulmer Artur J. , Duchrow Michael , Ernst Martin , Flad Hans‐Dieter , Hauschildt Sunna 
Published: March 2007

AbstractTo detect mRNA expression of nitric oxide synthase (NOS) isoforms in human monocytes/macrophages reverse transcription polymerase chain reaction (RT‐PCR) was used. mRNA was isolated from stimulated or unstimulated monocytes/macrophages and RT‐PCR was performed using oligonucleotide primers derived from mRNA sequences of either human endothelial constitutive (c) or human hepatocyte inducible (i) NOS. RT‐PCR of mRNA isolated from resting monocytes and macrophages resulted in the amplification of a cNOS specific mRNA fragment. When the cells were stimulated with lipopolysaccharide (LPS)/interferon‐γ (IFN‐γ) prior to mRNA extraction, RT‐PCR yielded an iNOS‐specific amplification product. Whereas the activation of both cell types was accompanied by expression of iNOS mRNA, the cNOS signal seemed to be diminished upon immunostimulation. Not only in purified human monocytes but also in the human monocytoid cell lines MonoMac 6, THP‐1, and U937 cNOS mRNA was detected. The data clearly demonstrate the presence of iNOS and cNOS mRNA in human monocytes/macrophages and provide the necessary tools to investigate the regulation of NO synthesis in these cell populations.
Soluble interleukin‐6 receptors released from T cell or granulocyte/macrophage cell lines and human peripheral blood mononuclear cells are generated through an alternative splicing mechanism
Authors: Horiuchi Sankichi , Koyanagiu Yoshio , Zhouu Yongwei , Miyamotou Hirokuni , Tanakau Yuetsu , Waki Michinori , Matsumoto Akiyoshi , Yamamotou Mikio , Yamamotof Naoki 
Published: March 2007

AbstractTo detect transcripts encoding the interleukin‐6 receptor (IL‐6R) molecule lacking the transmembrane (TM) domain, in various cell lines and peripheral blood mononuclear cells (PBMC), we used the polymerase chain reaction (PCR) with primer pairs that flank the TM domain and which were selected to generate a 398‐bp fragment. We detected 398‐bp and 304‐bp DNA molecules in the PCR products of the U1, J22HL60, MT‐2, MT‐4, U937 and HL60 cell lines and of PBMC isolated from several individuals. The sequencing analysis of both DNA molecules showed that a 94‐bp region consisting of the TM domain of IL‐6R was deleted in the 304‐bp molecule. Moreover, we detected a soluble (s) IL‐6R protein of 45 kDa in culture supernatants of the MT‐2, MT‐4 and U937 cell lines by radioimmunoprecipitation using specific antibodies against sIL‐6R. Our results indicate that active deletion of the TM domain by alternative splicing of mRNA represents one mechanism for release of sIL‐6R into the culture supernatants of cells, or into serum or urine.
Endocytosis of the β chain of interleukin‐2 receptor requires neither interleukin‐2 nor the γ chain
Authors: Hémar Agnès , Lieb Michéle , Subtil Agathe , Disanto James P. , Dautry‐Varsat Alice 
Published: March 2007

AbstractInterleukin‐2 (IL‐2) and IL‐2 receptors (IL‐2R) critically regulate the magnitude and duration of T cell expansion required in an immune response. Modulation occurs at the level of receptor number and affinity. IL‐2R is a multisubunit receptor which contains at least three chains, IL‐2Rα (p55), IL‐2Rβ (p70) and IL‐2Rγ (p64). Some components of high‐affinity receptors (αβγ) are continuously internalized in the absence as well as in the presence of IL‐2. From studies on other receptors, it is known that endocytosis of ligand‐receptor complexes is due to an intrinsic property of the receptor. However, the specific chains responsible for endocytosis of high‐affinity IL‐2 receptors have not been fully elucidated. IL‐2Rγ has been reported to be necessary for IL‐2 internalization, based on the fact that fibroblasts transfected with IL‐2Rα and ‐β do not internalize IL‐2. However, IL‐2 dissociates too rapidly from IL‐2Rαβ receptors to allow for its internalization. From the reported results on IL‐2 internalization in transfected fibroblasts, it cannot be concluded as to the respective roles of IL‐2Rβ and/or IL‐2Rγ in endocytosis. As modulation of receptor number is important for biological activity, we have attempted to define the chains responsible for receptor internalization.In this work, we have studied the endocytic properties of IL‐2Rβ. We demonstrate that IL‐2Rβ is constitutively endocytosed in a B cell line, derived from a X‐linked severe combined immunodeficiency patient, which lacks expression of IL‐2Rγ. IL‐2Rβ was also constitutively internalized in T and natural killer cell lines independently of IL‐2Rγ. These results suggest that IL‐2Rβ is endowed with endocytic capacity and carries internalization signals.
Differences in responsiveness to CD3 stimulation between naive and memory CD4+ T cells cannot be overcome by CD28 costimulation
Authors: Kuiper Heleen , Brouwer Miranda , de Boer Mark , Parren Paul , Van Lier René A. W. 
Published: March 2007

AbstractActivation of naive CD4+ T cells is essential for the induction of primary immune responses. However, this subset is less responsive to signaling via T cell receptor/CD3 (TcR/CD3) complex than memory CD4+ cells. For mitogenic activation of T cells, in addition to triggering of the TcR/CD3 complex, costimulatory signals are required that can be generated by surface structures present on the antigen‐presenting cells. We investigated here whether differences in responsiveness to TcR/CD3 stimulation of naive and memory cells can be overcome by the costimulatory pathway B7/CD28. Using a B7‐dependent system we show that even in the presence of optimal CD28 costimulation, CD4+ naive cells still have more stringent TcR/CD3 activation requirements than memory cells. Furthermore, titration of the B7 signal revealed that for activation of naive CD4+ cells a higher level of cross‐linking of CD28 molecules is required than for memory cells. Thus, our results show that at least two signals are required for activation of both CD4+ memory and naive cells, but that for activation of naive cells higher cross‐linking of both CD3 and CD28 molecules is necessary.