bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction of cutaneous stromal cells and γ/δ T cell receptor (TcR)‐positive cells. I. Vγ5−γ/γTcR+ T cells migrating from organ‐cultured murine skin proliferate by co‐culture with cutaneous stromal cells in the presence of interleukin‐2
Authors: Nakagawa Satoshi , Hara Masahiro , Seki Makiko , Yagita Hideo , Tagami Hachiro , Aiba Setsuya 
Published: March 2007

AbstractIt has been reported that Thy‐1+CD3+CD4−CD8− cells as well as Langerhans cells migrate from organ‐cultured murine skin into culture medium. We examined whether these Thy‐1+ populations of migrating cells were derived from Thy‐l+ dendritic epidermal T cells (Thy‐1+ DEC) and found that they were Thy‐1+CD3+ CD4−CD8−γ/ΔTcR+ (γΔ+T) cells but did not express Vγ/5TcR, which was used by a vast majority of Thy‐1+DEC Recently, a unique interaction between stromal cells and lymphohemopoietic progenitors has been reported in bone marrow and thymus. In this study, we established fibroblastoid cutaneous stromal cell (CSC) lines and clones from murine skin and examined the interaction between CSC and γδ+T cells. When these γδ+T cells were co‐cultured with CSC, a marked proliferation of small lymphoid cells was observed only in the presence of interleukin (IL)‐2. Neither CSC alone nor IL‐2 alone could induce a similar proliferation. Flow cytometry revealed that they were Thy‐1+CD3+ CD4−CD8−γ/5TcR− but Vγ5TcR−. Analysis of the major segments of their TcR by polymerase chain reaction demonstrated that Vγ1,Vγ2,Vγ4 and all of the Vδ chains from Vδ1 to Vδ7 were used without any predominant pattern. These data indicate the possible presence of yδ+T cells other thanVγ5TcR+Thy‐l+ DEC in the murine skin and the unique capacity of the CSC to support the growth of these migrating y/δ+ T cells.The nomenclature of murine T cell receptor γ chain is according to Reilly et al. (Nature 1986. 527:878). The relationship between the different nomenclature systems is summarized in Takagi et al. (J. Immunol. 1989. 747:2112).
In vivo activation of mouse dendritic epidermal T cells in sites of contact dermatitis
Authors: Kaminski Marek J. , Bergstresser Paul R. , Takashima Akira 
Published: March 2007

AbstractAdult mouse epidermis contains a population of dendritic,Thy‐l+,CD3+,CD4−, CD8− and T cell receptor (TcR) Vγ3/Vδ1+ leukocytes termed dendritic epidermal T cells (DETC). DETC isolated from skin and placed into culture will proliferative vigorously in response to T cell mitogens and T cell growth factors. In the present study, we examined whether DETC can be activated in situ by modulating their epidermal environment. Ear skin of CBA mice was painted with the chemical irritant, croton oil, and the epidermal cells (EC) isolated from such sites were then tested for proliferative responses to exogenous interleukin‐2 (IL‐2), in the absence of added mitogens. Cells from croton oil‐treated skin showed marked IL‐2 responsiveness, whereas cells from phosphate‐buffered saline‐treated skin failed to proliferate. IL‐2 responses were seen as early as 2 days after croton oil treatment and peaked between days 5 and 10. γδ TcR‐bearing cells, most likely resident DETC, were the major population to respond to IL‐2, since depletion of γδ TcR+ cells, but not γδ TcR+ cells, abolished that responsiveness, and since γδ TcR+ cell numbers increased markedly in the cultures that contained added IL‐2. These results indicate that DETC in normal skin, which are at a state of rest, may be activated when their residential epidermal environment is disrupted externally. This process of DETC activation may be a critical step in the maturation of DETC into effector leukocytes in vivo.
Pathogenic autoantibodies in the NZB mouse are specific for erythrocyte Band 3 protein
Authors: Barker Robert N. , De Oliveira Geraldo G. SÁ , Elson Christopher J. , Lydyard Peter M. 
Published: March 2007

AbstractNZB mice spontaneously develop autoimmune hemolytic anemia (AIHA). The red blood cell (RBC) autoantigen bound by pathogenic IgG autoantibodies, previously designated “X”, was identified by immunoprecipitation. Autoantibody eluted from the RBC of AIHA‐positive NZB mice precipitated a 105‐kDa antigen that was identical in apparent molecular mass to Band 3, the RBC anion channel protein. Furthermore, the immunoblotted antigen also reacted specifically with BRIC 132, a monoclonal antibody against Band 3. The results, therefore, demonstrate that Band 3 bears autoantigenic epitopes that are important in the pathogenesis of AIHA in the NZB mouse.
Presentation of mouse tum− P91A antigen from chimeric proteins with different subcellular localizations by class I molecules of the major histocompatibility complex
Authors: Godelaine Danièle , Van Pel Aline , Van Malderen Marianne , Beaufay Henri 
Published: March 2007

AbstractLike many antigens presented by class I molecules the mouse Ld‐binding turn−antigen P91A derives from a cytosolic protein. To decide how stringent this localization is for presentation to cytotoxic lymphocytes (CTL) the P91A template has been inserted in the cDNA of rat esterase ES‐10, a protein located in the endoplasmic reticulum (ER), and in the cDNA of mouse interleukin‐9, a secretory product of lymphocytes. The esterase construct was also engineered to replace the C‐terminal leucine by arginine, which causes secretion of the protein, or to delete the N‐terminal presequence, which prevents transfer of the nascent chain to the ER. After cell‐free transcription‐translation, or transfection in COS cells, the products of the chimeric cDNA had the expected size and localization; however, the truncated form of esterase remained undetected in COS cells. The various chimeric templates were transfected in Pl.HTR cells (H‐2d); upon challenge with Ld‐restricted anti‐P91A CTL the cells were lyzed almost as efficiently as cells transfected with the full‐length P91A cDNA. We conclude that peptide fragments that bind to class I molecules of the major histocompatibility complex can be generated in the ER.
Evidence for selective pressure in the appearance of monoclonal immunoglobulins during aging: Studies in M54 μ‐transgenic mice
Authors: Gueret Roland , Grandien Alf , Andersson Jan , Coutinho Antonio , Radl Jiri , Weksler Marc E. 
Published: March 2007

AbstractSerum monoclonal immunoglobulins (M‐Ig) appear during aging but little is known about the immunological factors which lead to their development. We have investigated whether such M‐Ig occur as a clonally random process or result from V‐region‐directed selective pressures. We have analyzed a μ‐transgenic mouse strain in which over 95% of all splenic B cells express the transgenic μ chain. All endogenous repertoire and unchain diversity are generated from the 5% of the B cells which express endogenous μ chains. Not one of the M‐Ig detected in these mice were of transgene origin alone; 11 of the 14 M‐Ig did not express a μ‐ chain and none of the μ chain containing M‐Ig expressed the transgene allotype alone. This observation suggests that the B cells giving rise to M‐Ig are heavily selected from among the small number of B cells which express endogenous Ig. The selective factors that might act on the endogenous B cell pools are discussed.
In vivo enhancement of the specific antibody response via the low‐affinity receptor for IgE
Authors: Heyman Birgitta , Tianmin Liu , Gustavsson Susanne 
Published: March 2007

AbstractThe ability of antigen‐specific IgE antibodies to modulate the in vivo antibody response was studied by comparing the antibody response in mice immunized with 2,4,6‐trinitrophenyl (TNP)‐specific monoclonal IgE followed by bovine serum albumin (BSA)‐TNP or with BSA‐TNP alone. The serum IgG antibody response against BSA, measured in enzyme‐linked immunosorbent assay ELISA, was enhanced up to 100‐fold in groups receiving IgE. The enhancement required specific interaction between IgE and antigen, since no effect was seen when unconjugated BSA was used as antigen. Polyclonal activation by IgE/antigen complexes did not occur. IgE given 24 h after specific antigen had no stimulatory capacity. Pretreatment of the mice with Fee receptor type II (FcϵRII)‐specific monoclonal antibody completely inhibited the IgE‐mediated enhancement. Thus, the data demonstrate for the first time an in vivo role for FcϵRII in enhancement of specific antibody production.
Phosphodiesterase inhibitor pentoxifylline, a selective suppressor of T helper type 1‐ but not type 2‐associated lymphokine production, prevents induction of experimental autoimmune encephalomyelitis in Lewis rats
Authors: Rott Ortwin , Cash Evelyne , Fleischer Bernhard 
Published: March 2007

AbstractThe phosphodiesterase inhibitor pentoxifylline (POX), which is known to have pharmacological effects in animal models of multiorgan failure and endotoxin‐mediated shock, was tested for its immunosuppressive potential on T lymphocyte activation in vitro and in vivo. POX was found to have a profound inhibitory effect on both mitogen‐ and antigen‐induced proliferation of CD4+ T cells in vitro. This inhibitory activity of the drug could be reproduced by treating T lymphocytes with cAMP analogues during stimulation. Responses of repeatedly in vitro stimulated cells were much more strongly inhibited by the drug and by cAMP analogues than responses of fresh resting lymphocytes. Furthermore, POX could drastically down‐regulate tumor necrosis factor regulate production and to a lesser extent interleukin (IL)‐2 secretion in activated T cells, but an excess of exogenous IL‐2 did not override the antiproliferative effect of the drug. In contrast, the same doses of POX had no inhibitory effect on spontaneous or induced IL‐4 and IL‐6 production by short‐term cultured T lymphocytes, indicating a selective sparing of T helper type 2 (Th2)‐associated lymphokine functions by the drug. To test a potential use of POX as an antiinflammatory agent in T cell‐mediated autoimmune disease, the influence of POX on myelin basic protein (MBP)‐induced experimental autoimmune encephalomyelitis (EAE) was assessed. The onset of EAE in Lewis rats could almost completely be abrogated by oral administration of POX during the induction phase of disease. Lack of clinical symptoms in POX‐treated animals coincided with a marked suppression of MBP‐specific T cell reactivity in vitro, without any evidence for a generalized impairment of T cell activity. Collectively, our data suggest the potential use of xanthine derivatives of the POX type as a supporting antiinflammatory therapeutic agent in Th1 CD4+ T cell‐mediated autoimmune diseases in animal models and possibly in man.
Reduced expression of major histocompatibility complex class I free heavy chains and enhanced sensitivity to natural killer cells after incubation of human lymphoid lines with β2‐microglobulin
Authors: Carbone Ennio , Stuber György , Andrée Sofia , Franksson Lars , Klein Eva , Beretta Alberto , Siccardi Antonio G. , Kärre Klas 
Published: March 2007

AbstractEnhancement of major histocompatibility complex (MHC) class I expression leads to protection from recognition by natural killer (NK) cells in several systems. MHC class I gene products can be expressed in different forms at the cell surface ‐ for example as “empty” β2‐microglobulin (β2m)‐associated heterodimers or free heavy chains. To study the role of different class I heavy chain forms in NK target interactions, we have used lymphoblastoid target cell lines preincubated with β2m. This was found to shift the equilibrium between β2m‐associated and nonassociated ‐ heavy chains in favor of the former. In parallel, there was a significant increase in NK sensitivity. The recognition of MHC class I‐deficient cell lines was not affected by β2m, arguing against a general nonspecific effect of fern on NK sensitivity. Our data indicate that protection against NK recognition correlates with target cell expression of free heavy chains (i.e. devoid of β2m) rather than with expression of complexes.
Induction of protective immunity against coronavirus‐induced encephalomyelitis: Evidence for an important role of CD8+ T cells in vivo
Authors: Flory Egbert , Pfleiderer Michael , And Albert Stühler , Wege Helmut 
Published: March 2007

AbstractCoronavirus MHV‐JHM infections of rats provide useful models to study the pathogenesis of virus‐induced central nervous system disease. To analyze the role of the immune response against defined MHV‐JHM antigens, we tested the protective efficacy of vaccinia virus (VV) recombinants expressing either the nucleocapsid (N) or the spike (S) protein. A strong protection was mediated in animals by immunization with recombinant VV encoding a wild‐type S protein (VV‐SWildtype), whereas VV recombinant expressing a mutant S354CR protein (VV‐S354CR) had no protective effect. Recombinant VV encoding N protein (VV‐N) induces a humoral and a CD4+ T cell response, but did not prevent acute disease regardless of the immunization protocol. In these experiments, challenge with an otherwise lethal dose of MHV‐JHM was performed prior to the induction of virus‐neutralizing antibodies and studies with the anti‐CD8+ monoclonal antibody, MRC OX8 showed that elimination of the CD8+ subset of T cells abrogates the protective effect. This result indicates that CD8+ T cells primed by recombinant VV expressing wild‐type S protein are a primary mechanism of immunological defense against MHV‐JHM infection in rats.
Interleukin‐12/T cell stimulating factor, a cytokine with multiple effects on T helper type 1 (Th1) but not on Th2 cells
Authors: Germann Tieno , Gately Maurice K. , Schoenhaut David S. , Lohoff Michael , Mattner Frank , Fischer Susanne , Jin Shen‐Chu , Schmitt Edgar , Rüde Erwin 
Published: March 2007

AbstractAt least two subsets of CD4+ T helper cell lymphocytes termed Th1 and T h, 2 exist in the mouse and probably in humans. They are characterized by the secretion of different lymphokines and by their functional behavior. Dysregulated expansion of one or the other subset may be one reason for the development of certain diseases. Thus, it is of importance to define the signals involved in the differentiation and activation of the two Th cell subsets. It is known and has been confirmed in this report that the cytokine interleukin (IL)‐1 acts onTh2 cells but not on Th1 cells. We now report that a previously identified cytokine which was provisionally termed T cell stimulating factor is identical with IL‐12 and exhibits a reciprocal behaviour to IL‐1. IL‐12 has several effects on Th1 cells. It can induce the proliferation of certain Th1 cells in combination with IL‐2. Synthesis of interferon (IFN)‐γ by Th1 cells can be triggered by IL‐2 plus IL‐12. In contrast to the IFN‐γ production observed after T cell receptor (TcR) CD3 stimulation of Th1 cells with lectin Concanavalin A the IFN‐γ production induced by IL‐12+IL‐2 is insensitive to the immunosuppressive drug cyclosporin A. Furthermore, IL‐12 enhances the TcR/CD3‐induced synthesis of IFN‐γ of several Th1 clones. Finally, IL‐12 (+ IL‐2) induces homotypic cell aggregation of Th1 clones. This type of cell aggregation depends on the participation of LFA‐1 and ICAM‐1 molecules. In all activation systems with Th1 cells no effect of IL‐1 was demonstrable. In contrast, only IL‐1 but not IL‐12 served as a co‐stimulatory signal for several Th2 cell lines activated via the TcR/CD3 complex.
A soluble, single‐chain Kd molecule produced by yeast selects a peptide repertoire indistinguishable from that of cell‐surface‐associated Kd
Authors: Abastado Jean‐Pierre , Ojcius David M. , Casrouge Armanda , Yeh Patrice , Schumacher Ton N. M. , Ploegh Hidde L. , Kourilsky Philippe 
Published: March 2007

AbstractPeptide binding to a soluble, single‐chain Kd protein produced by the yeast strain Kluyveromyces lactis, and to Kd molecules on Kd‐expressing cells (P815) was studied using radiolabeled Kd‐restricted peptides. The stability of the peptide‐Kd complexes formed was monitored in the absence and presence of unlabeled competitor peptides. Radioiodination of the Tyr anchor residue in position 2 of the peptide interferes with binding. A Kd‐biased peptide library and a modified antigenic peptide in which a second Tyr was added in positions 6 and 8, respectively, were therefore used to assay binding. Recombinant and cell‐associated Kd molecules are very similar in the following respects: the ease with which the proteins can be loaded with labeled peptide; the spectrum of peptides selected from a peptide library; the stability of the labeled peptide‐Kd complex formed; and the ability to partially dissociate the class 1‐peptide complex with exogenous, unlabeled peptides. These results imply that measurements of peptide binding to soluble Kd molecules are a reliable indicator of the peptide‐binding properties of Kd proteins on living cells. The large quantities of soluble recombinant Kd protein currently available represent an invaluable tool not only for dissecting the molecular mechanisms of antigen presentation but also for vaccinations and the design of T cell‐specific toxins.
Protection from insulin‐dependent diabetes mellitus is linked to a peptide transporter gene
Authors: Caillat‐Zucman Sophie , Bertin Eric , Timsit José , Boitard Christian , Assan Roger , Bach Jean‐François 
Published: March 2007

AbstractHLA class II association with insulin‐dependent diabetes mellitus (IDDM) is well established but is still difficult to map to a particular locus. Polymorphism of the genes coding for transporter associated with antigen processing (TAP1 and TAP2), and located in the HLA class II region, was studied in 167 IDDM patients (116 adult‐onset and 51 childhood‐onset patients) and 98 normal controls using oligotyping after genomic amplification. A dominant protective effect was observed for theTAP2*0201 allele [relative risk (RR)=0.3, corrected probability (pc) < 0.001]. Conversely, susceptibility to IDDM was associated with apparent homozygosity for the TAP2*0101 allele (RR=3.4, pc < 0.001). Protection was independent from but additive to the protection conferred by the DRB1*02 DQB1*0602 haplotype (RR=0.06, pc<0.05), and antagonistic to the DRB1*03 DQB1*0201 and DRB1*04 DQB 1*0302 haplotypes predisposing effect (RR=1.1, not significant), arguing in favor of an absence of linkage disequilibrium between TAP2 and HLA class II genes. This was assessed by x2 analysis. TAP1 allelic distribution was not different among diabetics and controls. A significant association was observed between the presence of TAP2*0101 and that of islet cell antibodies (p < 0.05). These data suggest that the TAP2 gene, which encodes protein required for delivery of antigen peptides to class I molecules in the endoplasmic reticulum, could modulate the autoimmune response leading to β cell destruction. From a practical point of view, they make the combined screening of HLA class II and TAP2 loci a highly valuable tool in IDDM prediction.
Enhancing effect of natural killer cell stimulatory factor (NKSF/interleukin‐12) on cell‐mediated cytotoxicity against tumor‐derived and virus‐infected cells
Authors: Chehimi Jihed , Valiante Nicholas M. , D'Andrea Annalisa , Rengaraju Manthrasalam , Rosado Zenaida , Kobayashi Michiko , Perassia Bice , Wolf Stanley F. , Starr Stuart E. , Trinchieri Giorgio 
Published: March 2007

AbstractNatural killer cell stimulatory factor (NKSF) or interleukin‐12 (IL‐12) is a heterodimeric cytokine with pleiomorphic effects on T and NK cells, including induction of lymphokine production, mitogenesis, and enhancement of spontaneous cytotoxic activity. Similarly to IL‐2, NKSF/IL‐12 enhances NK cell‐mediated cytotoxicity within a few hours and independently from induced proliferation. This effect is independent from other induced cytokines, because it is not prevented by antibodies neutralizing interferon (IFN)‐α, IFN‐β IFN‐γ, IL‐2 or tumor necrosis factor (TNF)‐α and, unlike the induction of IFN‐γ production by peripheral blood lymphocytes, it does not require HLA class II‐positive accessory cells. Enhanced cytotoxicity is accompanied by morphologic changes in NK cells, including a significant increase in the number of cytoplasmic granules. In addition to the previously described ability to enhance the cytotoxic activity of NK cells against tumor‐derived target cells, NKSF/IL‐12 is also a potent stimulator of cytotoxicity against virus‐infected cells, either fibroblasts acutely infected with herpes viruses or T cell lines chronically infected with human immunodeficiency virus‐1. NK cell‐mediated antibody‐dependent cytotoxicity or anti‐CD16 antibody‐redirected lysis is not significantly enhanced by NKSF/IL‐12. However, the ability of resting peripheral blood T cells to mediate anti‐CD3 antibody‐redirected lysis is enhanced by 18‐h incubation with NKSF/IL‐12, indicating that this lymphokine can modulate the cytotoxic capability of both NK and T cells.
Gene expression and secretion of cytokines and cytokine receptors from highly purified CD56+ natural killer cells stimulated with interleukin‐2, interleukin‐7 and interleukin‐12
Authors: Naume Bjørn , Johnsen Ann‐Charlotte , And Terje Espevik , Sundan Anders 
Published: March 2007

AbstractInterleukin (IL)‐2 IL‐7 and IL‐12 stimulate the generation of lymphokine‐activated killer activity and proliferation in natural killer (NK) cells by different mechanisms. In this study, we have compared the ability of IL‐2, IL‐7 and IL‐12 to induce expression of cytokines and cytokine receptors both at the gene and protein level. IL‐2 and IL‐12 stimulated the CD56+ NK cells to release significant amounts of soluble p55 and p75 tumor necrosis factor receptor (TNFR), whereas less amounts of soluble TNFR were detected in IL‐7‐stimulated cultures. The p55 and p75 TNFR mRNA were expressed in resting NK cells, and no further induction was observed after cytokine‐stimulation. Compared to the effects of IL‐2, IL‐7 induced lower, but substantial levels of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) mRNA, and IL‐7 was a more potent GM‐CSF‐inducing stimulus than IL‐12. IL‐12 induced higher levels of interferon‐γ (IFN‐γ) mRNA than did IL‐2, and IL‐7 only weakly influenced the IFN‐γ expression. In accordance with the mRNA studies, IL‐7 induced the secretion of high amounts of GM‐CSF and no or low levels of IFN‐γ, whereas high amounts of IFN‐γ and low levels of GM‐CSF were detected in supernatants from IL‐12‐stimulated NK cells. In conclusion, IL‐2, IL‐7 and IL‐12 differentially regulate expression of cytokines and cytokine receptors both at the gene and protein level.
Bacterial expression of a single‐chain Fv fragment which efficiently protects the acetylcholine receptor against antigenic modulation caused by myasthenic antibodies
Authors: Mamalaki Avgi , And Nikos Trakas , Tzartos Socrates J. 
Published: March 2007

AbstractMonoclonal antibodies (mAb) against the main immunogenic region (MIR) of the acetylcholine receptor (AChR) are very potent in inducing antigenic modulation of the AChR in animals and in muscle cell cultures. A recombinant antibody fragment of the rat anti‐MIR mAb198 was cloned by polymerase chain reaction and expressed as soluble single‐chain Fv fragment (scFv198) in E. coli and affinity purified. DNA sequencing was used to define the VH (IB) and VL (K2) chain gene usage. scFv198 was found immunologically and biologically active. Its binding affinity for the Torpedo AChR (KD=2 ± 0.6 nM) was very similar with that of the intact mAb198 (KD=1.8 ± 0.6 nM) while for the human AChR(KD=80.7 ± 16.6 nM) it was about four times lower than that of the intact mAb198 (KD=21.6 ± 6.6 nM). This fragment was capable of efficiently protecting the AChR in human cell cultures, against antigenic modulation caused by the intact mAb198 or by the antibodies from a myasthenic patient. The produced scFv198 fragment is, therefore, potentially useful in therapeutic applications for myasthenia gravis after appropriate genetic manipulations.