bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced frequency of mitogen‐responsive T cell precursors in old mice injected with thymosin α1
Authors: Frasca Daniela , Adorini Luciano , Doria Gino 
Published: March 2007

AbstractInjection of old mice with thymosin α1, a synthetic peptide consisting of 28 amino acid residues and exhibiting thymic hormone‐like activity, increases the splenic frequency of T cell precursors. Young (3‐month‐old) or old (19–20‐month‐old) mice received a single i.p. injection of thymosin α1 or of an equimolar amount of the N14 (N‐terminal amino acid residues 1–14) or C14 (C‐terminal amino acid residues 15–28) synthetic fragment of the thymosin α1 molecule and their spleen cells were assayed 3 days later under limiting dilution conditions to assess the frequency of mitogen‐responsive and interleukin 2‐producing T cells. Injection of thymosin α1 or of its N14 fragment increases the frequency of responsive T lymphocytes in old, but not in young mice whereas injection of the C14 fragment has no demonstrable effect in either young or old mice. These data are consistent with our previous observation that the biological activity of thymosin α1 is restricted to the N‐terminal half of the molecule and suggest that this peptide amplifies the pool of mitogen‐responsive and interleukin 2‐producing T cells in immunodeficient old mice.
Monoclonal anti‐allotype antibody towards BALB/c IgM Analysis of specificity and site of a V‐C crossover in recombinant strain BALB‐Igh‐Va/Igh‐Cb
Authors: Schüppel Ralph , Wilke Joachim , Weiler Eberhardt 
Published: March 2007

AbstractPolyclonal IgM obtained by fractionation of a BALB/c serum pool was used as the immunogen for C57BL/6 mice. Draining lymph nodes from selected animals donated cells for fusion with myeloma Sp‐2/0. Fifteen hybridomas were productive, and one (RS‐3.1) was cloned and the affinity‐purified product analyzed for its reactivity pattern by MOPC 104E‐enzyme‐linked immunosorbent assay inhibition. Among five BALB/c myelomas only TEPC 183 (IgM) was active, not those belonging to other Ig classes. Among normal sera from 8 mouse strains only those of BALB/c, DBA/2J and CBA/J showed inhibition.The recombinant strain BALB‐Igh‐Va/Igh‐Cb did not react, which shows that its Cμ stems from parental strain C57BL/6, and that therefore the recombination event had occurred 5′ of this gene.
An antigen‐independent physiological activation pathway for L3T4+ T lymphocytes
Authors: Germann Tieno , Huhn Helga , Zimmermann Frank , Rüde Erwin 
Published: March 2007

AbstractThe data presented in this report describe an antigen‐independent activation pathway leading to reinduction of proliferation of class II major histocompatibility complex (MHC)‐restricted murine T cell lines that after previous antigen‐specific stimulation reverted to a resting state. Antigen‐independent proliferation and interleukin 2 (IL 2)‐receptor expression occur in the presence of splenic accessory cells, exogenous IL 2 and a soluble factor(s) provisionally termed T cell‐stimulating factor(s) (TSF). Each of these components is essential for inducing growth. TSF is found in the supernatant of an autoreactive T cell line upon stimulation with syngeneic accessory cells. Neither TSF nor accessory cells can be replaced by IL1 and by some other cytokines. Monoclonal antibodies against class IIMHC molecules, the T cell receptor and L3T4 do not block this antigen‐independent stimulation. This demonstrates that the function of the accessory cell in this system is not MHC restricted and that the T cell receptor is also not involved. Furthermore, it is suggested that the blocking of L3T4 molecules by antibody will mediate a negative signal only if T cells are triggered via their antigen receptors.
Specific helper T cell reactivity against autologous erythrocytes implies that self tolerance need not depend on clonal deletion
Authors: Hooper D. Craig , Taylor Roger B. 
Published: March 2007

AbstractUsing a culture system which supports primary T cell proliferative responses to various antigens we have detected mouse red blood cell (RBC)‐reactive T cells in lymphoid tissues from untreated mice. The release of significant amounts of interleukin 2 (IL2) indicates that T helper (or helper/inducer) cells are activated by stimulation with RBC. Upon restimulation in vitro these cells proliferate specifically against mouse RBC with the kinetics and magnitude characteristic of a secondary response. Since autologous RBC are tolerated in vivo in spite of the presence of such specifically reactive T helper cells, these findings imply that self tolerance, even to certain nonse‐questered antigens, may depend largely on regulatory mechanisms rather than on clonal deletion or inactivation.
Protein kinase C‐activating phorbol esters augment expression of T cell receptor genes
Authors: Noonan Daniel J. , Isakov Noah , Theofilopoulos Argyrios N. , Dixon Frank J. , Altman Amnon 
Published: March 2007

AbstractTumor‐promoting phorbol esters (PE) can modulate cellular functions and cell surface determinant expression in a variety of cell types, including T lymphocytes, presumably by activating the enzyme, protein kinase C (PKC). To examine whether PKC might be involved in regulating the expression of genes encoding the antigen‐specific T cell receptor (TCR), we cultured the murine thymoma line, EL4, in the presence of 12‐O‐tetradecanoylphorbol 13‐acetate (TPA) and analyzed the expression of TCR α or β‐chain genes by Northern blots. TPA stimulation of an interleukin 2 (IL 2)‐producing variant, EL4+, induced a 3–4‐fold increase in TCR β, but not α, chain mRNA. Maximal increase was obtained with 3 ng/ml TPA and 12 h of stimulation. This effect appeared related to PKC activation because other tumor‐promoting PE known to be PKC activators, but not inactive PE, induced the same increase. TPA stimulation of EL4+ cells also induced de novo expression of the IL 2 gene and subsequent secretion of this lymphokine. However, the increased expression of the TCR β‐chain gene and the induction of the IL 2 gene were not linked since (a) expression of TCR β‐chain mRNA was increased to a similar degree in EL4+ and IL 2‐nonproducing EL4− sublines, and (b) cyclosporin A selectively blocked TPA‐induced IL 2‐gene expression in EL4+ cells without affecting the increase in TCR β‐chain mRNA. These findings suggest that PKC activation, an event that supposedly occurs after antigen‐mediated triggering of the TCR, can regulate the expression of at least some of the genes encoding this receptor.
Proliferation of Ly‐1 B cells in autoimmune NZB and (NZB × NZW)F1 mice
Authors: Wofsy David , Chiang Nancy Y. 
Published: March 2007

AbstractSpontaneous autoimmune disease in NZB and (NZB × NZW)F1 (B/W) mice is associated with a spectrum of lymphoproliferative abnormalities, but the relationship between autoimmunity and lymphoproliferation is poorly understood. Lymphomas occur commonly in NZB mice, but they appear to be rare in B/W mice, perhaps because B/W mice die of murine lupus before the lymphomas are evident. We recently reported that autoimmune disease in B/W mice could be reversed by weekly treatment with monoclonal antibodies to the L3T4 antigen on “helper/inducer” T cells. This has enabled us to examine the evolution of lymphoproliferation in B/W mice that survive beyond the usual life span, both in long‐term survivors of treatment with anti‐L3T4 and in the occasional B/W mouse that spontaneously survives beyond 1 year of age. We find that all of these mice develop marked proliferation of a distinct subpopulation of B cells that express the Ly‐1 antigen in low density. These Ly‐1+ B cells account for a 2‐10‐fold increase in the number of splenic, lymph node and peripheral blood lymphocytes. The Ly‐1 B cells in individual mice are restricted in their expression of immunoglobulin light chains, suggesting a clonal origin. NZB mice develop similar proliferation of Ly‐1 B cells, suggesting that this is due to underlying genetic and/or viral factors in NZB and B/W mice, and that it is not the result of treatment with anti‐L3T4. Although recent studies have implicated Ly‐1 B cells in the production of autoantibodies, proliferation of Ly‐1 B cells in B/W mice was not associated with production of anti‐DNA antibodies or with any paraprotein.
Activation of B lymphocytes by Epstein‐Barr virus/CR2 receptor interaction
Authors: Masucci Maria G. , Szigeti Robert , Ernberg Ingemar , Hu Cheng‐Po , Torsteinsdottir Sigurbjörg , Frade Raymond , Klein Eva 
Published: March 2007

AbstractEpstein‐Barr virus (EBV) infects and transforms human B lymphocytes. The virus receptor was shown to be identical to the complement receptor CR2. The consequences of EBV/CR2 receptor interaction on B lymphocyte activation were analyzed by infection of B cells with the transforming (B95‐8) and the nontransforming (P3HR1) virus strains and with UV‐inactivated B95‐8 virus.Similar to mitogens and antibodies against surface IgM and CR2 receptor, transforming and nontransforming EBV induced the release of leukocyte migration inhibitory factor (LIF). LIF production occurred early after infection and was not affected by irradiation of the B95‐8 virus with doses of UV‐light which prevented the expression of viral functions. B lymphocytes infected with UV‐inactivated virus responded to T cell‐derived B cell growth factors.The results demonstrate that binding of EBV to the CR2 receptor activates the B cells. Progression of the infected cells in the activation pathway required helper cell‐derived factors or signals provided by the intact viral genome. The nontransforming P3HR1 virus induced a low level of RNA synthesis and increase of cell size and major histocompatibility complex class I antigen expression. Only the transforming virus induced expression of EBV nuclear antigens and cellular DNA synthesis.
A functional idiotypic network of T helper cells and antibodies, limited to the compartment of “naturally” activated lymphocytes in normal mice
Authors: Coutinho António , Marquez Carlos , Araujo Paulo M. F. , Pereira Pablo , Toribio Maria Luisa , Marcos Miguel Angel R. , Martinez‐A Carlos 
Published: March 2007

AbstractAs shown previously, idiotype (Id) sharing between anti‐2,4,6‐trinitrophenyl T helper (Th) cells and antibodies in BALB/c mice results from immunoglobulin (Ig)‐dependent selection of the T cell repertoire. In contrast, a clonotype defined by the same F6(51) anti‐Id antibody is expressed by C57BL/6 anti‐(4‐hydroxy‐3‐nitrophenyl)acetyl Th cells independently of Ig influences. We have now used these systems to test the hypothesis that Ig‐dependent Th cell repertoire selection occurs in the compartment of “naturally” activated lymphocytes.“Naturally” activated or resting splenic L3T4+ cells were separated from normal BALB/c and C57BL/6 mice and tested, either directly or after in vitro priming, in hapten‐specific helper assays for expression of the clonotope defined by the F6(51) anti‐Id antibody. The results show the selective expression of the antibody‐dependent T cell Id in the “naturally” activated helper cell compartment. In contrast, when the T cell Id is expressed in the absence of Ig‐dependent selection, it is only detected in the resting helper cell repertoire. Furthermore, BALB/c “natural” IgM antibodies with anti‐Id specificities similar to F6(51) show functionally relevant interactions with syngeneic “naturally” activated Th cells. These are also characterized by high paratopic/Id degeneracy, as compared to helper cells obtained by conventional immunization. These results demonstrate repertoire differences between the set of (resting) lymphocytes participating in immune responses, vs. those “internally” activated in normal individuals. They also suggest the importance of Id network interactions in the compartment of “naturally” activated T and B cells.
Soluble factors secreted by naturally occurring suppressor cells that interfere with in vivo graft‐vs.‐host disease and with T cell responsiveness in vitro
Authors: Knaan‐Shanzer Shoshan , Van Bekkum Dirk W. 
Published: March 2007

AbstractA potent immunosuppressive factor (SUF) is found in the supernatant of short‐term cultures of unstimulated thymocytes or spleen cells of neonatal mice and rats and in culture medium of hybridoma cell lines established by fusing neonatal mouse spleen cells with T lymphoma cells (the BW 5147 line). In vitro incubation of spleen cells with SUF suppresses the acute in vivo graft‐vs.‐host disease, normally induced by allogeneic spleen cells in lethally irradiated mice. Incubation of bone marrow cells with SUF does not affect the hemopoietic stem cells. The addition of SUF to mixed lymphocyte reaction cultures strongly suppresses lymphocyte proliferation. The non‐species‐restricted inhibition of cell proliferation induced by SUF is shown not to be due to toxicity or nonspecific interference with DNA synthesis.Molecular size fractionation of crude SUF revealed two active moieties: a large moiety of molecular mass > 100 kDa and a small moiety of < 3 kDa. The high kDa moiety mediates T cell unresponsiveness both in vivo and in vitro. In vitro studies revealed that this moiety primarily affects an early event in the proliferative response to alloantigen and mitogen, that prevents interleukin 2 (IL 2) receptor expression and, consequently, blastogenesis and DNA duplication. It does not affect, however, the synthesis of IL 2. The suppressive activity of the low kDa moiety can be demonstrated only in in vitro systems. Pre‐treatment of donor lymphocytes with this fraction cannot prevent graft‐vs.‐host disease mortality. The inhibition of cell proliferation induced by this fraction in vitro is most likely due to interference with the utilization of IL 2, as suggested by its suppressive effect on the proliferation of CTLL‐2 cells (an IL 2‐dependent cell line).
Expression of the Fcγ receptor on Ly‐1+ B lymphocytes
Authors: Dexter Charles M. , Corley Ronald B. 
Published: March 2007

AbstractThe expression of IgG Fc receptor (FcR) molecules was examined on Ly‐1+ B cells and B cells tumors. FcR molecules were found on a representative Ly‐1+ B cell lymphoma of the pre‐B and as well as of the mature cell B phenotypes. The expression of the FcR did not change on these cells during their differentiation to B cells or to antibody‐secreting cells, respectively. Ly‐1+ B cells were found at low frequency (∼2%) in the spleens of normal mice, and in the peritoneal cavity where their representation was greater. The frequency of Ly‐1+ B cells declined after birth, although their numbers increased in both organs. These Ly‐1+ B cells expressed the FcR molecule throughout ontogeny. Furthermore, the amount of FcR expressed on Ly‐1+ B cells was similar to the levels expressed on their “conventional” (Ly‐1−) B cell counterparts. The FcR was also found on Ly‐1+ B cells from autoimmune mice. The significance of the expression of FcR molecules on Ly‐1+ B cells is discussed.
Activation of T cells by cross‐linking an anti‐CD3 antibody with a second anti‐T cell antibody: mechanism and subset‐specific activation
Authors: Walker Christoph , Bettens Florence , Pichler Werner J. 
Published: March 2007

AbstractBinding of anti‐CD3 antibody BMA030‐F(ab′)2 to T cells is not able to induce T cell proliferation even after additional cross‐linking by plastic‐bound goat anti‐mouse Ig antibodies (panning) and addition of either interleukin (IL)1 or IL2. In search for agents able to complement the signals provided by BMA030‐F(ab′)2, several antibodies directed against CD2, CD4, CD5, CD6 and CD8 were used. Neither of these caused T cell proliferation either by themselves or when simply added together with BMA030‐F(ab′)2. However, if BMA030‐F(ab′)2 and any other of these anti‐CD2, CD4, CD5, CD6 or CD8 antibodies were cross‐linked, then proliferation of T cells occurred. The mitogenic effect of cross‐linking BMA030‐F(ab′)2 and a second anti‐T cell antibody is dependent on the presence of monocytes or exogenously added IL2. The enhancing effect of monocytes could not be replaced by addition of IL1, suggesting that other soluble factors or monocyte contact might be involved in induction of activation signals.The mechanism leading to this mitogenic effect is dependent on combining cross‐linking of BMA030 with the second anti‐T cell antibody, whereby the second antibody appears to act as an “anchor” for the CD3 antibody, controlling and/or changing the signal transduction via the CD3 structure. This “anchor” hypothesis could be substantiated by the following observations: (a) the best stimulatory signals were obtained at a BMA030/anti‐T cell antibody ratio of 1:1; (b) the effect is independent of the antibody isotype and the epitope recognized by the second antibody; (c) the binding of BMA030 and separate cross‐linking of the anti‐T cell antibody was not sufficient to trigger T cell mitogenesis; (d) immobilization by direct binding of the CD3 antibody alone or of the CD3 and second membrane structure/antibody complex separately was not sufficient to stimulate T cell proliferation.A further interesting aspect of this finding is the fact that a selective T cell stimulation is possible, since cross‐linking BMA030‐F(ab′)2 plus anti‐CD4 antibodies induced a selective stimulation of T4 cells, while cross‐linking BMA030‐F(ab′)2 plus anti‐CD8 activated solely T8 cells. It is thus possible to selectively activate T cell subsets in vitro.
Anti‐HLA‐class II monoclonal antibodies inhibit polyclonal B cell differentiation in vitro at the accessory cell level
Authors: De Rie Menno A. , Kabel Peter , Sauerwein Robert W. , Van Lier Rene A. W. , von Dem Borne Albert E. G. Kr. , Melief Cornelis J. M. , Miedema Frank 
Published: March 2007

AbstractWe produced and characterized a panel of anti‐HLA class II monoclonal antibodies (mAb) to study the inhibition of T cell‐dependent B cell differentiation. The newly produced mAb belonged to different isotypes and subclasses, and recognized at least two different nonpolymorphic HLA class II determinants. We found that anti‐HLA class II mAb inhibited the pokeweed mitogen (PWM)‐ and interleukin 2‐driven T cell‐dependent IgM synthesis, but did not affect the phorbol myristate acetate‐, phytohemagglutinin‐, anti‐T3‐ or PWM‐induced T cell proliferation. Moreover, when the mAb were tested in a monocyte‐independent B cell differentiation assay in which T cells are activated by insoluble anti‐T3 mAb in the absence of accessory cells, no effect was seen on IgM synthesis. These data indicate that inhibition of T cell‐dependent B cell differentiation by anti‐HLA class II mAb is caused by interference with an accessory cell function essential for B cell differentiation.
Limiting dilution assay for human B cells based on their activation by mutant EL4 thymoma cells: total and anti‐malaria responder B cell frequencies
Authors: Wen Li , Hanvanich Mattana , Werner‐Favre Christiane , Brouwers Nicolette , Perrin Luc H. , Zubler Rudolf H. 
Published: March 2007

AbstractThe analysis of human B cell responses at the clonal level (limiting dilution assay) is still technically difficult. In the present study we report on a culture system that leads to activation, proliferation and differentiation into antibody‐secreting cells (ASC) of about 90% of B cells from peripheral blood or spleen. In this system, B cells are cultured in the presence of (a) a mutant subclone of the mouse thymoma EL4 for B cell activation and (b) human T cell plus macrophage supernatant as source of proliferation and differentiation factors. ASC precursors generating clonal responses of IgM only, IgM plus IgG, or IgG only occurred at a ratio of about 6:3:1. The mean clone size was 380 cytoplasmic Ig+ cells; the mean amount of Ig secreted per clone was 20 ng.Furthermore, it has been found using this system that a considerable proportion of peripheral blood B cells from individuals with a history of malaria infection could generate clones of anti‐malaria (Plasmodium falciparum) ASC (range of 0.1 to 1%, n = 6). In a control group of blood donors the corresponding frequencies were 10 times lower (range of 0.01 to 0.1%, n = 9). These results show that the EL4 culture system can be applied to the investigation of the human B cell specificity repertoire and of priming effects such as result from infectious disease.
Mutual tolerization of histoincompatible lymphocytes
Authors: Rammensee Hans‐Georg , Bevan Michael J. 
Published: March 2007

AbstractT lymphocytes react strongly against foreign major histocompatibility complex encoded class I antigens by destroying incompatible tissue in vivo, and by generating cytotoxic T lymphocytes (CTL) in vitro. The absence of reactivity against self antigens may be due to clonal deletion of self‐reactive T cells during their ontogeny in the thymus. The functional clonal deletion of mature T cells in the periphery was described recently: CTL recognizing antigen on other CTL are eliminated (Rammensee et al., Immunol. Today 1985. 6: 41). Hence, in a normal immune system only autoreactive cells would be eliminated. Here we show that injection of lymphocytes into class I‐incompatible mice leads to abrogation of host anti‐donor as well as donor anti‐host reactivity, leaving a mixed population of host and donor T cells reactive against third‐party antigens. The results demonstrate the existence of a peripheral failsafe mechanism for the elimination of autoaggressive CTL. Whether this failsafe mechanism is actually used under physiological conditions is a different question.
“In vivo” activated splenic T cells are refractory to interleukin 2 growth “in vitro”
Authors: Bandeira António , Larsson Eva‐Lotta , Forni Luciana , Pereira Pablo , Coutinho António 
Published: March 2007

AbstractNaturally activated T lymphocytes present in normal mouse spleen were studied for direct reactivity to interleukin 2 (IL 2) and for binding of anti‐IL 2 receptor (IL 2R) antibodies or radiolabeled IL 2. The majority of large‐sized splenic T lymphocytes are IL 2R−; thus, at the most one third of large L3T4+ T cells and of large Lyt‐2+ T lymphocytes bind (weakly) anti‐IL 2R antibodies; furthermore, most IL 2R+ cells in the normal spleen are actually Lyt‐2−, L3T4−. Total large splenic lymphocytes do not express more than an average of 150 high‐affinity IL 2R/cell. Such cell populations, as well as large T cells enriched from them, failed to proliferate exponentially in the presence of recombinant IL 2, but did not suppress the IL 2‐dependent proliferative responses of small T cells activated in the same cultures. In vivo activation of small T cells, in concanavalin A‐treated irradiated syngeneic hosts, also results in refractoriness to growth in recombinant IL 2. In addition, these cells remain insensitive to ligands such as concanavalin A, phorbol myristate acetate and ionomycin, in the presence or absence of IL 2. These results question the role of IL 2 as a growth factor of in vivo activated splenic T lymphocytes, or else indicate that most of these are terminally differentiated cells.