bluuebunny/crossref_metadata_2025_split huggingface dataset:
Major histocompatibility complex (MHC) control of CD4 T cell subset activation. II. A single peptide induces either humoral or cell‐mediated responses in mice of distinct MHC genotype
Authors: Murray Joseph S. , Pfeiffer Christiane , Madri Joseph , Bottomly Kim 
Published: March 2007

AbstractCD4 T cells activated in vivo in response to human collagen type IV (hCol IV) resemble either T helper type 1 (Th1) or Th2 cells depending on the major histocompatibility complex (MHC) class II genotype of the responding mice. H‐2s mice were shown to selectively activate Th1‐like cells, releasing interleukin (IL 2) and interferon‐γ in response to hCol IV, whereas H‐2b,d mice were shown to selectively activate Th2‐like cells, releasing IL 4 and IL 5 in response to hCol IV. These results suggested that MHC class II regulated the type of effector function observed during an immune response. It was of interest to determine if the functional difference observed between the CD4 T cells of the two strains was due to the presentation of different peptides of the hCol IV molecule by the two MHC class II molecules. The present results demonstrate that a single peptide of the collagen IV molecule will elicit a Th1‐like response in H‐2s strains and Th2‐like responses in H‐2b,d strains, as was observed when using the intact hCol IV molecule. Furthermore, the failure to generate Th1‐like responses in H‐2b,d could be overcome by increasing the dose of this peptide in vitro. Compared to H‐2s, the Th1‐like response in H‐2b required 100 times the amount of peptide to reelicit an equivalent response. These data suggest that a single peptide of hCol IV can control the type of effector response observed.
Protection from lethal graft‐vs.‐host disease by donor stem cell repopulation
Authors: Rozendaal Lawrence , Pals Steven T. , Melief Cornelis J. M. , Gleichmann Ernst 
Published: March 2007

AbstractGraft‐vs.‐host reaction (GVHR) induced in non‐irradiated F1 mice with DBA/2J parental spleen and lymph node (LN) cells usually does not lead to acute GVH disease (GVHD). This contrasts with the GVHR induced in other parent‐F1 combinations involving both major histocompatibility complex (MHC) class I and class II differences between donor and host. Most signs of acute GVHD in non‐irradiated F1 mice relate to immunodeficiency following destruction of the lymphohemopoietic system of the host, which leads to wasting and death due to infections. This sequence of events is prevented when donor lymphoid cells, originating from grafted stem cells, repopulate the destroyed lymphohemopoietic system of the host. To examine whether a “silent” repopulation of the F1 host by donor stem cells might underly the absence of clinical signs of acute GVHD when GVHR is induced with DBA/2J lymphoid cells, GVHR was induced with LN cells, which do not contain stem cells. Indeed. GVHR induced in (C57BL/10 × DBA/2J)F1 (BDF1) mice with 80 × 106 DBA/2J LN cells led to acute GVHD. Signs of acute GVHD such as wasting and death did not occur when donor stem cells, from an inoculum of DBA/2J spleen and LN cells, were allowed to repopulate the lymphehemopoietic system of the host. The effect of donor stem cells on clinical signs of acute GVHD was more apparent when (B10.D2 × DBA/2J)F1, instead of DBA/2J, lymphoid cells were used to induce GVHR. The detection of alloreactive anti‐host cytotoxic T lymphocyte (CTL) activity during acute GVHD induced with DBA/2J donor lymphoid cells supports the hypothesis that such CTL contribute to the destruction of the host immune system in acute GVHD.
Two signals are involved in polyclonal B cell stimulation by T helper type 2 cells: a role for LFA‐1 molecules and interleukin 4
Authors: Lohoff Michael , Koch Andreas , Röllinghoff Martin 
Published: March 2007

AbstractT helper cell type 2 (Th2) cells when triggered by antibodies to CD3 acquire the capacity to stimulate the polyclonal proliferation of syngeneic, resting B cells. Here, we tested the ability of various monoclonal antibodies (mAb) to block the B cell proliferation‐inducing potential of such activated Th2 cells. We demonstrate that anti‐interleukin 4, as well as anti‐LFA‐1 antibodies interfere with the T‐B cell interaction. In kinetic studies, anti‐LFA‐1 was found to be operative during the first half and anti‐interleukin 4 during the second half of the 48‐h culture period. This defines at least two different steps in B cell triggering by Th2 cells. In addition, the data imply that the T‐B cell interaction involves an additional structure, namely an activation molecule, on the T cell surface.
Activation of natural killer cells via the FcγRIII (CD16) requires initial tyrosine phosphorylation
Authors: Ståhls Anders , Heiskala Marja , Mustelin Tomas , Andersson Leif C. 
Published: March 2007

AbstractTriggering of the FcγRIII (CD16) on natural killer (NK) cells by monoclonal antibodies or antibody‐coated target cells stimulates a rapid phospholipase C (PLC)‐mediated hydrolysis of inositol phospholipids and results in subsequent delivery of the lytic hit. The role of initial tyrosine phosphorylation in these events was investigated with a tyrosine protein kinase (TPK) inhibitor, genistein. At doses that inhibited CD16‐triggered tyrosine phosphorylation of substrates in intact cells, genistein did not influence serine/threonine phosphorylation or target cell binding but prevented PLC activation, cell‐mediated cytotoxicity and antibody‐dependent cellular cytotoxicity. These findings indicate that tyrosine phosphorylation is an early and critical event during receptor‐mediated activation of the lytic machinery.
Cationic residues in pathogenic anti‐DNA autoantibodies arise by mutations of a germ‐line gene that belongs to a large VH gene subfamily
Authors: O'Keefe Theresa L. , Datta Syamal K. , Imanishi‐Kari Thereza 
Published: March 2007

AbstractThe F1 progeny of autoimmune NZB and normal SWR mice uniformly develop severe and accelerated lupus nephritis. The (SWR × NZB)F1 mice produce an oligoclonally expanded population of nephritogenic anti‐DNA autoantibodies that share a recurrent cross‐reactive idiotype (Id564), use highly homologous VH genes and surprisingly have the CH region allotype of the normal SWR parent. From extensive library analyses, we isolated 15 SWR germ‐line genes which are most closely related to the pathogenic autoantibody VH564 gene and which also belong to the NPb subfamily of J558 VH genes. We found that the pathogenic VH genes are probably somatic variants of a SWR germ‐line VH gene, SW6—3, and they have several basic amino acid substitutions, in addition to those already present in the SW6—3 germ‐line gene. Since these pathogenic autoantibodies are not detectable in the sera of the normal SWR mice despite the presence of the SW6—3 gene, strong selection and expansion of B cells expressing the SW6—3 VH gene is probably occurring in (SWR × NZB)F1 lupus‐prone mice. We also isolated eight germ‐line genes from the NZB mouse which are homologous to SW6—3. The autoimmune NZB parent that rarely develops nephritis lacks the SW6—3 gene, but has several highly homologous germ‐line VH genes that would encode less cationic antibodies. These results establish a correlation between structure and pathogenic potential of VH genes.
Natural mouse IgG reacts with self antigens including molecules involved in the immune response
Authors: Berneman Armand , Ternynck Thérèse , Avrameas Stratis 
Published: March 2007

AbstractIgG isolated on protein A‐Sepharose from pools of normal sera from various mouse strains were examined by immunoblotting for reaction with self antigens. Homogenates of the major mouse organs, i.e. brain, skin, spleen, kidney, adrenals, thymus, heart, muscle and liver were used as the source of autoantigens. IgG stained at least 220 bands on the immunoblots. The antigens corresponding to these bands were tentatively identified by molecular mass estimation and referenced to computerized mouse protein data banks. IgG mainly recognized enzymes but it also stained intracellular structural constituents and surface molecules implicated in the functioning of the immune system. The validity of this identification was confirmed by analyzing purified antigens from mouse or other animal species by immunoblotting and enzyme immunoassays. Furthermore, extracts of 125I‐surface‐labeled cells were immunoprecipitated with IgG in the liquid phase or immobilized on beads. The proteins precipitated migrated to the same positions as those precipitated by specific monoclonal antibodies (mAb), such as class I α chain and β2‐microglobulin, class II α and β chains, CD3, CD4 and CD8 antigens. The results obtained with several enzyme immunoassay procedures using cell membrane extracts, specific mAb and normal IgG further supported the specific interaction of IgG with Ia, CD4 and CD8 molecules. Affinity chromatography indicated that at least 20% of normal mouse IgG possess polyreactive autoantibody function. Dissociation constants of these IgG were calculated for some autoantigens and found to be in the range of 2 × 10−6−7 × 10−6 M. It is concluded that normal mouse IgG exhibit autoreactivities similar to those previously described for IgM.
T cell subset‐specific expression of antigen receptor β chains in α chain‐transgenic mice
Authors: Ivars Fredrick 
Published: March 2007

AbstractA large number of Vβ8 gene‐encoded cDNA were analyzed from peripheral CD4+ and CD8+ T cell subsets of T cell receptor (TcR) α chain‐transgenic mice. This analysis demonstrates that a limited repertoire of TcR β chains are co‐expressed with the transgenic α chain. Most importantly, certain Vβ8‐Jβ combinatons were found exclusively in one of the subsets and, in some cases, subset‐specific differences were localized to the VDJ junctional region of the β chain genes. In contrast, CD4−CD8−transgenic T cells, as well as CD4+ and CD8+ T cells from normal littermate controls, were found to express diverse β chain repertoires. The present study suggests that β chains with distinct structural characteristics are expressed in the CD4+ and CD8+ subsets, respectively. Moreover, the data suggest that the same structural constraints do not apply to the population of CD4−CD8− transgenic T cells.
Allorecognition of isolated, denatured chains of class I and class II major histocompatibility complex molecules. Evidence for an important role for indirect allorecognition in transplantation
Authors: Dalchau Rosemarie , Fangman Josef , Fabre John W. 
Published: March 2007

AbstractClassical RT1‐A class I and RT1‐B class II major histocompatibility complex (MHC) molecules were purified from DA (RT1av1) spleens, and the individual chains separated and purified by preparative polyacrylamide gel electrophoresis in sodium dodecyl sulfate. LEW (RT11) rats were immunized with the pure class I heavy chain, the RT1‐B α chain and the RT1‐B β chain with the aim of priming to indirect allorecognition (i.e. after processing and presentation of DA MHC chains on LEW antigen‐presenting cells) in the absence of any priming to direct allorecognition (i.e. to whole, undenatured, dimeric DA MHC molecules). LEW rats immunized with each of the three DA MHC chains produced alloantibodies to these chains, suggesting that indirect allorecognition did occur, because of the requirement for cognate recognition of B cells by T helper cells. This also demonstrated polymorphism of all three chains between the DA and LEW strains. The antibodies to the isolated, denatured MHC chains did not react to the whole MHC molecules on DA cells, with the possible exception of very weak reactions in some class I heavy chain‐immunized rats. DA skin grafts placed on LEW recipients immunized with each of the DA MHC chains were rejected in an accelerated fashion. Following DA skin grafting, there was an accelerated production of antibodies to whole, undenatured class I MHC molecules, even in the LEW rats preimmunized with RT1‐B α and RT1‐B β chains. These data suggest that indirect allorecognition can play an important role in the effector mechanisms of allograft rejection, and demonstrate T helper priming as one possible mechanism whereby this might be effective.
γ/δ T cell antigen receptors expressed on tumor‐infiltrating lymphocytes from patients with solid tumors
Authors: Nanno Masanobu , Seki Hidetoshi , Mathioudaki George , Suzuki Ryuzi , Itoh Kyogo , Ioannides Constantin G. , Suzuki Satsuki , Chen Pei‐Feng , Platsoucas Chris D. 
Published: March 2007

AbstractThe expression of γ/δ T cell antigen receptors (TcR) in T cell lines or clones derived from tumor‐infiltrating lymphocytes (TIL) from patients with solid tumors was investigated. γ/δ TcR T cell lines were derived from TIL from patients with Wilms tumor, sarcoma or metastatic melanoma by stimulation with autologous tumor cells alone and recombinant interleukin 2 and they exhibited nonspecific cytotoxicity against autologous and allogeneic tumor cells, or cells of the K562 or the MEL21 tumor cell lines. Two T cell lines were derived from a patient with Wilms tumor. One of them expressed a non‐disulfide‐linked γ/δ TcR using the 60‐kDa γ chain, whereas, the other expressed a disulfide‐linked γ/δ TcR. A T cell line was derived from a patient with sarcoma and expressed a disulfide‐linked γ/δ TcR, whereas, a T cell line derived from a patient with melanoma expressed a non‐disulfide‐linked γ chain of 62 kDa. Several T cell clones were developed from patients with metastatic melanoma or Wilms tumor and expressed either disulfide‐ or non‐disulfide‐linked γ/δ TcR. Northern analysis of RNA from certain of these clones revealed a full‐length γ chain transcript, whereas, the α or β chain transcripts were either absent or truncated. These T cell clones exhibited nonspecific cytotoxicity. Both disulfide‐ and non‐disulfide‐linked TIL T cell lines and clones expressed the δ TCS1 determinant. γ/δ TcR+ cells in freshly prepared TIL from these patients were present in low proportions (<5%) and their δTCS1/δ1 ratios were within the range observed in the peripheral blood of normal donors. These results demonstrate that both disulfide‐and non‐disulfide‐linked γ/δ TcR are expressed on T cell lines and clones derived from TIL from solid tumors. Non‐disulfide‐linked γ/δ TcR using the 56–66‐kDa γ chain are frequently found on TIL‐derived T cell lines and clones. These 56–66‐kDa γ chains are rarely expressed on T cell lines or clones derived from peripheral blood lymphocytes of normal donors.
Interleukin 2 receptor targeted fusion toxin (DAB486‐IL‐2) treatment blocks diabetogenic autoimmunity in non‐obese diabetic mice
Authors: Pacheco‐Silva Alvaro , Bastos Marcus G. , Muggia Robert A. , Pankewycz Oleh , Nichols Jean , Murphy John R. , Strom Terry B. , Rubin‐Kelley Vicki E. 
Published: March 2007

AbstractInsulin‐dependent diabetes mellitus (IDDM) is strikingly similar in the non‐obese diabetic (NOD) mouse and humans. In IDDM, the systematic autoimmune destruction of insulin‐producing β cells within the pancreas is dependent on autoreactive T cells. This autoimmune process can be accelerated by transferring spleen cells from diabetic donors into irradiated syngeneic NOD mice. In a previous study we established that interleukin 2 receptor (IL 2R)‐bearing cells propagated from pre‐diabetic NOD mice promote IDDM. Therefore, we reasoned that specific elimination of IL 2R+ T cells should abort the diabetogenic process. T cell expressing IL 2R can be selectively destroyed with a diphtheria toxin‐related IL 2 fusion protein (DAB486‐IL‐2). We set DAB486‐IL‐2 the challenging task of preventing fulminant IDDM accelerated by the adoptive transfer of diabetic spleen cells. Eight weeks after the adoptive transfer only 10% and 20% of NOD mice treated with 10 and 5 μg/day of DAB486‐IL‐2, respectively, became diabetic while 100% control mice (vehicle buffer) became diabetic within 5 weeks. A dose of 1 μg/day of DAB486‐IL‐2 had no protective effect. Although the protection conferred by DAB486‐IL‐2 is not permanent, it is maintained for at least 4 weeks following cessation of treatment. Furthermore, even though these NOD mice do eventually become diabetic, the tempo of expression and severity of diabetes, as assessed by the level of hyperglycemia, is dramatically reduced. Although histologic examination of pancreas revealed minimal degree of mononuclear infiltrate within the islets in both groups, the vehicle control mice had fewer islets per section indicating many islets had already been destroyed. In addition, spleen cells from diabetic NOD mice which were pre‐treated with DAB486‐IL‐2 (10μ/day) for 1 week lost their ability to transfer disease. Taken together, these studies strongly support the concept that IL 2R‐bearing T cells are essential for the induction of IDDM and suggest that DAB486‐IL‐2 would be a promising therapeutic approach in the treatment of human IDDM.
The effect of an immunoglobulin μ transgene on B cell maturation
Authors: Iacomini John , Imanishi‐Kari Thereza 
Published: March 2007

AbstractIn μ 17.2.25‐transgenic (M54) mice the absolute number of surface IgM (slgM) B cells in lymphoid organs is drastically reduced compared to normal C57BL/6 mice and a high frequency of B cells express the immunoglobulin (Ig) encoded by the transgene rather than endogenous Ig on the surface. To determine the effect of a μ trangene on B cell development, adoptive cell transfers were performed using μ transgenic (M54) bone marrow and fetal liver cells. The data presented support the following conclusions: (a) adult transgenic bone marrow contains functional B cell precursors able to mature and repopulate the spleen and peritoneum of recipient mice. The relative frequency of transgene (sIgMa) and endogenous (sIgMb) surface sIgM‐positive B cells reconstituted by transgenic bone marrow in allotype‐matched C57BL/6 recipients is the same as in the M54 donors; (b) serum analysis indicates that transgenic bone marrow donor cells can reconstitute B cells in congenic and severe combined immunodeficient (SCID) recipient mice; (c) transgenic fetal liver cells are not a richer source of precursors for B cells expressing endogeneous Ig; (d) in transgenic mice sIgM+ B cells are not restricted to the CD5+ phenotype, however, the relative frequency of sIgMb B cells that are CD5+ is higher in transgenic than normal mice; and (e) bone marrow cells from adult normal and transgenic mice are able to generate CD5+ B lymphocytes in the spleen and peritoneum of allotype‐congenic and neonatal SCID recipient mice.The results indicate that the presence of a complete μ heavy chain transgene does not result in a selective developmental block of “conventional” bone marrow‐derived pre‐B and B cells.
Diversity of T cell receptor α and β chain genes expressed by human T cells specific for similar myelin basic protein peptide/major histocompatibility complexes
Authors: Giegerich Gerhard , Pette Martin , Meinl Edgar , Epplen Jörg T. , Wekerle Hartmut , Hinkkanen Ari 
Published: March 2007

AbstractT cell receptor (TcR) α and β nucleotide sequences involved in the human autoreactivity to myelin basic protein (MBP) were studied by screening cDNA libraries derived from 11 independent T lymphocyte clones (TCC) established from multiple sclerosis patients and healthy donors. The TCC with defined MBP peptide specificity and HLA‐DR restriction expressed multiple TcR. Even TCC recognizing the same human MBP peptide [amino acids (aa) 139–153] in identical or very similar HLA‐DR context expressed diverse TcR. Two TCC which recognized peptide aa 139–153 equally well in the context of both HLA‐DR2a and ‐DR1 molecules used distinct TcR α but identical β chains.The knowledge of TcR β and TcR α chain sequences of human MBP‐specific T cells will allow studies correlating structure and function of TcR and their targets in MBP autoreactivity. This may have an impact on the development of immunotherapies in multiple sclerosis.
Constraints in antigen processing result in unresponsiveness to a T cell epitope of hen egg lysozyme in C57BL/6 mice
Authors: Kim Byung S. , Jang Yong‐Suk 
Published: March 2007

AbstractT cell hybridoma clones were derived after fusion of BW‐5147 parent cells with lymphocytes from C57BL/6 mice injected with phosphorylcholine (PC)‐hen egg lysozyme (HEL) conjugates. Several T cell hybridomas were preferentially reactive with PC‐HEL over unconjugated HEL, and a particular clone (PC‐H4.1) was further analyzed. This T cell hybridoma clone could respond to its maximal level toward unconjugated HEL only when the dose of HEL was increased to 5–10‐fold of the PC‐HEL concentration. Interestingly, this clone was not stimulated by unfolded HEL (by S‐carboxymethylation) to the level of PC‐HEL. A synthetic peptide representing the amino acid position 47‐61 of HEL, which is known to be non‐immunogenic upon HEL injection in C57BL/6 mice, was able to stimulate the hybridoma only to a level comparable to that induced by unconjugated HEL. The T cell response to this synthetic peptide required an additional antigen‐processing step, based on its inability to stimulate T cells after treatment of antigen‐presenting cells with leupeptin, chloroquine or paraformaldehyde. Deletion of a single C‐terminal amino acid residue of HEL 47–61 (arginine) significantly enhanced (10–100‐fold of HEL47–61) the T cell reactivity and abrogated the necessity of further antigen processing. These results suggest that the lack of a T cell response to a certain epitope may not be due to the lack of a T cell repertoire reactive to the epitope. In some cases, the unresponsiveness may be due to the difficulty in generating the particular epitopes. Taken together, modification of the lysozyme molecule with PC conjugation may facilitate further antigen processing of HEL to generate an optimal epitope for the nonresponder mice.
Immunoglobulin production in severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood mononuclear cells
Authors: Abedi Mohammad R. , Christensson Birger , Islam Khalid B. , Hammarström Lennart , Edvard Smith C. I. 
Published: March 2007

AbstractImmunodeficient C.B‐17 scid/scid (SCID) mice were reconstituted with human peripheral blood mononuclear cells and analyzed for humoral immunity. The majority of adoptively transferred animals had serum levels of 1–4 mg/ml of human IgG 8–12 weeks after i.p. reconstitution with 20 × 106 PBMC, whereas the IgM and especially IgA concentrations were considerably lower. The half‐lives of human IgG, IgM, and IgA in SCID mice were 12 days, 36, and 23 hours, respectively. Furthermore, IgA was rapidly secreted into bile indicating that the low IgA concentration was mainly caused by a high turnover rate. IgG subclass distribution in mouse serum was similar to that found in the donor serum. Irradiation with 3 Gy prior to adoptive transfer resulted in increased levels of human IgG early after reconstitution, whereas both IgM and IgA concentrations were impaired. A polyclonal serum Ig pattern was found 4 weeks after transfer of human cells later frequently followed by a predominance of oligoclonal bands. Unexpectedly, oligoclonal bands were also found using donors with a negative Epstein‐Barr virus serology. Human cells were found to reside in the peritoneal cavity for several months. Within 2 weeks of reconstitution, human cells were also identified in lymphoid structures in the vicinity of the liver hilus with a later spread to other lymphoid organs. Homing of human cells to skin and gut was not seen.