bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunoglobulin heavy chain variable region family usage is independent of tumor cell phenotype in human B lineage leukemias
Authors: Deane Miriam , Norton John D. 
Published: March 2007

AbstractDuring B cell development, immunoglobulin heavy chain (IgH) variable region (VH) genes are rearranged and expressed in a programed manner and accumulating evidence suggests recurrent utilization of developmentally restricted VH genes in malignant B lymphoid populations. We have used polymerase chain reaction gene amplification in conjunction with a panel of VH family‐specific amplimers to directly compare the repertoire of VH region rearrangement in mature, CD5+ B cell chronic lymphocytic leukemia with that in immature, CD5 B lineage acute lymphoblastic leukemia. The results revealed a diverse pattern of VH family utilization common to both disease groups in which VH regions most proximal to the IgH joining locus were preferentially rearranged relative to their family sizes with recurrent utilization of several known developmentally restricted VH genes in close to germ‐line configuration. These results indicate that biased VH family usage is independent of tumor cell phenotype in B lineage leukemias. This bias may reflect similar stages or compartments in normal B lymphopoiesis from which diverse types of B cell malignancy may arise. Moreover, since blast cells in acute lymphoblastic leukaemia do not express functional immunoglobulin, we infer that the tumor cell‐associated VH family repertoire is determined through antigen‐independent mechanisms.
Glycosylation of IgG, immune complexes and IgG subclasses in the MRL‐lpr/lpr mouse model of rheumatoid arthritis
Authors: Bond Angela , Cooke Anne , Hay Frank C. 
Published: March 2007

AbstractThe MRL‐lpr/lpr (MRL/lpr) mouse spontaneously develops a disease syndrome which, in many respects, is similar to human rheumatoid arthritis. These mice develop joint inflammation, circulating rheumatoid factors and immune complexes. We now show that the parallel with human disease extends to a glycosylation defect which is observed on IgG from rheumatoid arthritis patients. Using the lectins ricin and Bandeiraea simplicifolia II we have found that terminal N‐acetylglucosamine is clearly raised in MRL/lpr IgG. Increased exposure of galactose was also detected, indicating that a second glycosylation site must be present on these molecules. Polyethylene glycol‐precipitated IgG complexes bound significiantly more of each lectin than did free IgG, indicating that the changes in glycosylation were associated with complex formation. The sugar abnormality was most marked in the IgG2a/IgG3 fraction from protein A IgG subclass chromatography. Our results suggest that the IgG glycosylation defect seen in rheumatoid arthritis is apparent in the MRL/lpr mouse and may contribute, through complex formation, to the pathological processes in the rheumatoid syndrome.
Ca2+ influx in human T lymphocytes is induced independently of inositol phosphate production by mobilization of intracellular Ca2+ stores. A study with the Ca2+ endoplasmic reticulum‐ATPase inhibitor thapsigargin
Authors: Gouy Hélène , Cefai Daniel , Christensen Soren Brogger , Debré Patrice , Bismuth Georges 
Published: March 2007

AbstractThapsigargin (TG), a sesquiterpene lactone and non‐phorbol 12‐myristate 13‐acetate tumor promoter, stimulates a rapid increase in intracellular free Ca2+ ([Ca2+]i) in human T lymphocytes clone P28. The [Ca2+]i response to TG is sustained in the presence of 1 mM extracellular Ca2+, while it becomes transient in Ca2+‐free medium suggesting that TG activates both the release of Ca2+ from intracellular stores and the entry of Ca2+ from extracellular spaces. TG‐induced Ca2+ influx is completely abolished after cell depolarization caused by increased extracellular concentrations of K+. The rise in [Ca2+]i stimulated by TG occurs in the absence of detectable production of inositol phosphates. Moreover, TG does not alter the early biochemical events of T cell activation triggered through the CD2 or the CD3 T cell antigens. Indeed, both inositol phosphate production and intracellular pH increase induced by specific monoclonal antibodies (mAb) remain unchanged after TG treatment. These data suggest that in human T lymphocytes TG releases Ca2+ from an intracellular pool by a mechanism which is independent of the phospholipase C metabolic pathway. Preincubation with TG of T cell clone P28 empties both the CD2 and the CD3‐sensitive intracellular Ca2+ pool(s). Conversely, prestimulation of T cell clone P28 by CD3 or CD2‐specific mAb inhibits the Ca2+‐mobilizing effect of TG. Thus it appears that TG and CD2‐or CD3‐specific mAb mobilize Ca2+ from common Ca2+ pool(s). Taken together, these results demonstrate that Ca2+ influx in human T cells may be linked to mobilization of intracellular Ca2+ pools and by a mechanism independent of phosphoinositide hydrolysis. They further indicate that the release of intracellular Ca2+ pool(s) may play a major role in the opening of cell membrane Ca2+ channels observed during the CD2‐ or CD3‐induced stimulation of human T lymphocytes.
Age‐related decrement in cytotoxic T lymphocyte (CTL) activity is associated with decreased levels of mRNA encoded by two CTL‐associated serine esterase genes and the perforin gene in mice
Authors: Bloom Eda T. , Umehara Hisanori , Bleackley R. Chris , Okumura Ko , Mostowski Howard , Babbitt Jane T. 
Published: March 2007

AbstractThe age‐related decline in cytotoxic T lymphocyte (CTL) activity has been recognized for many years. Age‐related alterations in several immunologic events have been suggested to be partly or completely responsible for this decline. We had previously demonstrated (Bloom et al., Cell. Immunol. 1988. 144: 440) in mice that a deterioration in the lytic mechanism may be at least in part responsible for the decline in CTL activity. We now report that this decline correlates with an age‐related decrease in serine esterase activity released into the supernatant medium in the process of generating CTL. Northern analyses were then used to examine the effect of age on expression of genes encoding for perforin and two CTL‐associated serine esterases. The products of all three of these genes have all been postulated to play roles in CTL‐mediated lysis. We show that the expression of all three of these genes appears to decline with age in the process of generating allogeneic CTL. These alterations in gene expression correlated both with diminished cytolytic and released esterase activities generated by mixed leukocyte culture in spleen cells of old mice compared to young. The age‐related decline in gene expression could not be attributed to shifts in T cell subsets, but CD8+ cells generated by allogeneic stimulation of nylon wool‐passed spleen cells from old mice expressed significantly less cytolytic activity than those from young. This report is the first demonstration of an age‐related decrease in expression of a functionally related group of genes. In addition, these findings are compatible with the suggested roles for perforin and serine esterase release in CTL‐mediated target cell lysis.
Porcine γ/δ T lymphocyte subsets differing in their propensity to home to lymphoid tissue
Authors: Saalmüller Armin , Hirt Werner , Reddehase Matthias J. 
Published: March 2007

AbstractThree types of Tcell receptors (TcR) γ/δ were identified in swine, all of which are disulfide‐bonded cell surface heterodimers. The first, a 38/40‐kDa molecule, is related to the TcR γ/δ of sheep and cattle, and defines in swine a subset of CD4−CD8− T lymphocytes that is enriched in the circulatingT lymphocyte pool. The other two receptors are private to swine. The second, a 37/40‐kDa molecule, is expressed by the major subset of CD2−CD4−CD8− T lymphocytes that is neither enriched in nor excluded from lymphoid tissue. By contrast, the third type of TcR γ/δ, a 40/46‐kDa molecule, is found on CD2+CD4−CD8− T lymphocytes accumulating in lymphoid tissue. Thus, TcR γ/δ T lymphocyte subsets differing in homing propensity are typified by the expression of distinct molecular forms of the TcR γ/δ.
HLA‐DQ molecules and the control of Mycobacterium leprae‐specific T cell nonresponsiveness in lepromatous leprosy patients
Authors: Ottenhoff Tom H. M. , Walford Charlotte , Nishimura Yasuharu , Reddy N. B. B. , Sasazuki Takehiko 
Published: March 2007

AbstractThe major histocompatibility complex (MHC) controls of the outcome of the immune response to T cell‐dependent antigens by dictating whether T cell responsiveness will result (MHC‐immune response [Ir] genes) or alternatively T cell nonresponsiveness will occur, possibly through the activation of suppressor cells (MHC‐immune suppression [Is] genes).In mice, I‐A molecules typically restrict antigen‐specific helper T cells. In contrast, H‐2 I‐E molecules have been reported to control nonresponsiveness to a variety of antigens through antigen‐specific suppressor cells. In analogy, HLA‐DR molecules are the dominant restriction elements for helper Tcells in man. This forces the question whether DQ molecules may be involved in controlling nonresponsiveness in man, e.g. through suppression. In one system, T cell nonresponsiveness to Schistosoma japonicum, evidence has been presented supporting this notion. We have now used a second system, Mycobacterium leprae‐specific T cell nonresponsiveness, that is typically found in lepromatous leprosy patients.We find positive but limited evidence for a role for HLA‐DQ molecules in controlling Tcell nonresponsiveness to M. leprae of the 22 nonresponder patients tested, 4 showed a proliferative T cell response to M. leprae after the addition of DQ‐ but not DR‐specific mAb to the cell cultures. In one of the four BCG nonresponders, anti‐DQ mAb had a similar effect.
Uptake of antigen by afferent lymph dendritic cells mediated by antibody
Authors: Harkiss Gordon D. , Hopkins John , McConnell Ian 
Published: March 2007

AbstractDendritic cells isolated from sheep afferent lymph were examined for their ability to bind soluble protein and peptide antigens labeled with fluorescein both in in vitro assays and following intradermal injection of antigen in vivo. Analysis of dendritic cells by flow cytometry revealed weak direct binding of proteins and peptide antigens. However, the degree of uptake was greatly enhanced in the presence of specific antibody in vitro or if antigen was injected intradermally into antigen‐primed sheep. About 60% of dendritic cells possessed the ability to take up antigen in both the in vitro and in vivo experiments. The uptake of antigen occurred very rapidly, reaching maximum values in terms of cell numbers and fluorescence intensity in less than 5 min in vitro and 20–40 min following in vivo challenge. Both sheep IgG subclasses could mediate this effect, but F(ab')2 fragments were ineffective. Procedures adopted to remove complement components from the in vitro test mixtures did not result in any reduction in the binding of antigen by dendritic cells. Two‐color flow cytometry analysis of the dendritic cell population further showed that 43% of cells taking up the antigen/antibody complexes were CD1+, suggesting a relationship between these cells and Langerhans' cells or other dendritic cells in skin. The results, thus, indicate that approximately two thirds of sheep afferent lymph dendritic cells bind antigen/antibody complexes via an Fc receptor, a mechanism which could be important in the accentuated accessory function of these cells known to occur following secondary antigen challenge.
Parasite‐accessory cell interactions in Theileriosis. Antigen presentation by Theileria annulata‐infected macrophages and production of continuously growing antigen‐presenting cell lines
Authors: Glass Elizabeth J. , Spooner Roger L. 
Published: March 2007

AbstractTheileria annulata, a protozoan parasite of cattle, infects major histocompatibility complex (MHC) class II+ cells, particularly macrophages, and transforms them into continuously growing cell lines. We examined the effects of parasitism by T. annulata on antigen‐presenting cell function. T. annulata‐infected cells (TaH) presented ovalbumin (as measured by [3H]thymidine incorporation) to both resting autologous bovine T cells and ovalbumin‐specific bovine CD4+ T cell lines. However, the former cells were also stimulated by TaH without exogenous antigen although to a lesser degree than in the presence of antigen. This “nonspecific” proliferation was not seen with the ovalbumin‐specific T cell lines. The magnitude of response by resting T cells in the presence of antigen, to TaH or purified peripheral blood monocytes, was essentially similar. However, on a per cell basis fewer TaH were required. Considerably greater proliferation to antigen was seen with the ovalbumin‐specific T cell lines in the presence of TaH compared to monocytes and again fewer TaH were required to elicit a response. The kinetics of processing did not appear to be substantially altered in TaH and the increased proliferation may be due to the elevated MHC class II expression of these cells. Genetic restriction studies with the T cell lines indicated that the restricting elements used to present ovalbumin by TaH were the same as those used by monocytes, as identified by an isoelectric focusing technique. The continuously growing cell lines provide us with a unique model for investigating parasite‐accessory cell interactions in theileriosis. The augmented antigen presenting cell activity of TaH may play an important role in the pathogenesis of the disease. TaH will also provide us with a valuable resource for our antigen presentation studies. In particular, the enhanced antigen presentation by TaH enabled us to detect responses to lower levels of antigen, often an important consideration for experiments where the quantity of antigen available is the major limiting factor.
Inhibition of the mixed lymphocyte reaction by T cell vaccination
Authors: Lohse Ansgar W. , Mor Eitan , Reshef Tamara , Meyer Zum Karl‐Hermann , Büschenfelde  , Cohen Irun R. 
Published: March 2007

AbstractImmunization with attenuated activated autoreactive T cell lines and clones induces a response in syngeneic animals which can induce protection or recovery from autoimmune disease. This process has been termed T cell vaccination. The aim of the present study was to investigate the effect of immunization with MHC‐reactive T cells on the mixed lymphocyte reaction (MLR). By injecting attenuated activated T cells primed for an alloantigen, we markedly reduced the MLR in both rats and mice. This depression appeared to be mediated by active suppression; lymphoid cells from T cell‐vaccinated animals suppressed the MLR responsiveness of T cells from naive animals. Suppression of the MLR was not restricted to the major histocompatibility complex (MHC) alleles used to prime the animals from which the T cell vaccines were prepared; the MLR to other MHC allelic stimulator cells was also suppressed. This MHC‐unrestricted suppression could not be attributed to an anti‐ergotypic response to non‐MHC‐linked activation markers on T cells; an anti‐ergotypic response augmented rather than suppressed the MLR. We herein propose that T cell vaccination might influence the MLR by suppressing the responses of diverse T cells which bear shared T cell receptor idiotypes.
Immunization of susceptible hosts with a soluble antigen fraction from Leishmania major leads to aggravation of murine leishmaniasis mediated by CD4+ T cells
Authors: Bogdan Christian , Schröppel Klaus , Lohoff Michael , Röllinghoff Martin , Solbach Werner 
Published: March 2007

AbstractThis study was performed in order to define Leishmania major antigens that function as disease‐modulating immunogens in susceptible BALB/c mice. A soluble leishmanial antigen preparation (S‐SLA) derived from highly infective stationary‐phase L. major parasites was fractionated by preparative gel electrophoresis. In vitro, the low molecular mass fraction (<31 kDa) of S‐SLA fraction D (FR D) was found to be a potent stimulator of L. major‐specific Th1 and Th2 helper cell clones. In vivo, immunization with FR D induced a Th2‐biased immune response in BALB/c mice as determined by the numbers of splenic CD4+ cells secreting interleukin 4 and interferon‐γ according to limiting dilution analyses. In addition, FR D caused significant disease exacerbation in parasiteinfected susceptible mice as assessed by the local lesion development and the numbers of parasites in lymph nodes and spleen. This effect was observed after local subcutaneous application of FR D as well as after systemic immunization (intrasplenic or intraperitoneal). Transfer experiments revealed, that the disease‐aggravating effect of FR D was mediated by CD4+ T cells.From these results it is concluded that leishmanial protein preparations exist that not only fail to induce protective antiparasitic immunity, but can mediate disease exacerbation, independently of the primary application site of the immunogen. The existence of such structures may serve the parasite as a means to evade the host's immune attack and may also have implications for the development of vaccines.
Effects of prolonged incubation of rat peritoneal mast cells with compound 48/80
Authors: Levi‐Schaffer Francesca , Riesel‐Yaron Naomi 
Published: March 2007

AbstractRat peritoneal mast cells (MC) co‐cultured on a monolayer of 3T3 fibroblasts (MC/3T3) were continuously exposed to compound 48/80 for 14 days. As early as 2 days following continuous exposure to compound 48/80, the MC/3T3 appeared as a heterogeneous population, with various MC appearing partially or fully degranulated or intact; this morphological pattern continued throughout the duration of the experiment. MC/3T3 remained functionally active as demonstrated by their ability to secrete histamine 15 min after each replacement with fresh medium containing compound 48/80, although this capacity diminished towards the end of the 14‐day experiment. Concomitant with the histamine release, a significant increase in cellular histamine pools was observed. When MC/3T3 continuously exposed to compound 48/80 for 7 or 14 days were acutely challenged with anti‐IgE antibodies, they were able to secrete histamine and prostaglandin D2 in amounts similar to those produced by control MC. In contrast, when these cells were challenged on day 7 or 14 with a higher dose of compound 48/80 or with substance P, the release of histamine was partially inhibited. Our results indicate that continuous in vitro exposure to compound 48/80, and the resulting MC degranulation product histamine, does not adversely affect the ability of MC/3T3 to synthesize histamine and to respond to activation stimuli of a related secretagogue for 7 days and a non‐related one for at least 14 days.
The neonatally T cell receptor 2‐suppressed rat : lymphocyte subset composition and immune reactivity
Authors: Schlipköter Eva , Hünig Thomas 
Published: March 2007

AbstractRats were injected intraperitoneally from birth on with a mouse monoclonal antibody (R73) to a constant determinant of the rat T cell receptor (TcR)2. Throughout the observation period (6 months), TcR2+ cells in peripheral lymphoid organs and blood were absent in treated animals with the exception of few (< 10%) cells with a tenfold reduced TcR2 density; peripheral TcR2−CD3+ cells, i.e. most likely TcR1+ T cells, were increased in frequency. Among thymocyte subpopulations, only those expressing the TcR2 at a high level were reduced in number. The lack of a visible effect on immature thymocytes may, however, be due to the fact that despite high serum levels, thymic R73 determinants were incompletely saturated.Spleen and lymph node cells from TcR2‐suppressed rats were completely unresponsive in mixed lymphocyte reaction (two fully allogeneic haplotypes tested) even in the presence of interleukin 2. Reactivity to the T cell mitogen concanavalin A was, in contrast, only partially reduced. Since rat TcR1 cells are activated by concanavalin A, these results suggest that the TcR1 cells present in TcR2‐suppressed rats are functional, but do not respond to foreign major histocompatibility complex antigens at a high frequency, a finding of possible importance for immunosuppression with anti‐TcR2 monoclonal antibody in human allografting. Neonatally TcR2‐suppressed rats were unable to respond to the strong T‐dependent antigen keyhole limpet hemocyanin administered intraperitoneally in alum with B. pertussis. Thus, in the absence of peripheral TcR2 cells, the numerically expanded TcR1 T cells are not capable of providing help for B lymphocytes.
Heavy and light chain sequences of four monoclonal antibodies that bind galactosylgloboside (GalGb4)
Authors: Snyder James G. , Weng Nanping , Yu‐Lee Li‐Yuan , Marcus Donald M. 
Published: March 2007

AbstractWe recently described IgM monoclonal antibodies directed against the glyco‐spingolipid galactosylgloboside (GalGb4; Marcus, M. D. et al., Arch. Biochem. Biophys. 1988. 262: 620). We now present the nucleotide and deduced amino acid sequences of the heavy and light chains of these antibodies. The antibodies were generated in a single fusion, their heavy as well as their light chains are almost identical, and they appear to be clonally related. The light chains were encoded by Jx5 and a Vx gene belonging to the Oxl family, but they are only 93% homologous to the most closely related germ‐line gene, and they are probably encoded by a germ‐line gene that has not yet been identified. The heavy chains were all encoded by VH441 and JH2, and have identical N segments. The VH441 germ‐line gene encodes a potential glycosylation site at Asn58 in the complementarity‐determining region 2. This site, which has been retained in all VH441‐encoded monoclonal antibodies sequenced previously, was mutated out by a single base change in all four anti‐GalGb4 antibodies.
Chemical and immunochemical identification of the second major rabbit immunoglobulin λ chain polypeptide bearing c7 epitopes
Authors: Jaton Jean‐Claude , Hayzer David J. , Frutiger SéVerine , Hughes Graham J. , Young‐Cooper Glendowlyn O. , Mage Rose G. 
Published: March 2007

AbstractThe purification of λ chain‐containing IgG fraction from pooled sera of Basilea rabbits, which were bred and selected for the expression of a high level of λ chains positive for c7 but negative for c21, was carried out. On the basis of specific binding to anti‐c7 antiserum, the c7 λ chain fraction in serum IgG was shown to account for up to 70% of the total immunoglobulin light chains, the remaining 30%, bearing the expected κ2 bas isotype. Peptide mapping of the mixed light chains (λ + κ2 bas) followed by microsequencing of the constant region fragments indicated that the Cλ region originated from the cDNA sequence derived from a c7+,c21− Basilea rabbit (i.e. identical to gene Cλ6), as described in the preceding report (Hayzer, D. J. et al., Eur. J. Immunol. 1990. 20: 2707). In addition, a synthetic peptide encompassing residues 139–159 of the constant region derived from the predicted sequence of gene Cλ6 was shown to partially inhibit the c7‐anti‐c7 binding reaction in a sensitive enzyme‐linked immunosorbent assay. Taken together, the chemical and immunochemical data clearly demonstrate that gene Cλ6 indeed encodes c7 epitopes.