bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of specific immunity to human colon carcinoma by anti‐idiotypic antibodies to monoclonal antibody CO17‐1A
Authors: Herlyn Dorothee , Ross Alonzo H. , Iliopoulos Dimitrios , Koprowski Hilary
Published: March 2007

Anti‐idiotypic antibodies (Ab2) to murine monoclonal antibody (mAb) CO17‐1A (Ab1), which defines an antigen associated with human colon carcinoma, were produced in goats. The Ab2 inhibited binding of Ab1 to colon carcinoma cells, and purified tumor antigen inhibited binding of Ab1 to Ab2. The Ab2 elicited in rabbits anti‐anti‐idiotypic antibodies (Ab3) that bound to cultured human cells of various tissue origins with a binding pattern identical to that of Ab1. Moreover, both Ab1 and Ab3 bound to the isolated tumor antigen, and the Ab3 lysed human colon carcinoma cells in culture in the presence of rabbit complement. Thus, Ab2 raised to mAb CO17‐1A are candidates for use in immunotherapy trials in cancer patients.
Induction of interleukin 1 secretion and of tumoricidal activity in macrophages are not closely related phenomena
Authors: Keller Robert , Keist Ruth
Published: March 2007

Rat bone marrow‐derived mononuclear phagocytes (BMMΦ), induced to differentiate in vitro and homogeneous with respect to the cell lineage, were interacted with various macrophage‐activating agents. The effect of these agents on the secretion of interleukin 1 (IL 1) activity and on the development of tumoricidal capacity was comparatively assessed. The findings show that IL 1 secretion is considerably enhanced by macrophage‐activating factor and by recombinant interferon‐γ but remained unaffected or was even suppressed by heat‐killed C. parvum or Listeria monocytogenes. In contrast, lymphokines as well as C. parvum and Listeria were similarly potent in inducing in BMMΦ a tumoricidal state. The findings indicate that induction of IL 1 secretion and of tumoricidal activity are not necessarily closely linked phenomena.
Reduced production of interleukin 2 and interferongamma and enhanced helper activity for IgG synthesis by cloned CD4+ T cells from patients with AIDS
Authors: Maggi Enrico , Macchia Donatella , Parronchi Paola , Mazzetti Marcello , Ravina Adriana , Milo Domenico , Romagnani Sergio
Published: March 2007

Purified T lymphocytes (E rosetting cells) isolated from peripheral blood (PB) of four patients with acquired immune deficiency syndrome (AIDS) were cloned under culture conditions (phytohemagglutinin plus interleukin 2) which allow clonal expansion of most T lymphocytes. A total number of 101 T cell clones (37 CD4+ and 64 CD8+) from PB of AIDS patients and of 188 T cell clones (115 CD4+ and 73 CD8+) from PB of four normal controls were obtained and tested for their helper function as well as for their capacity to release lymphokines. Unstimulated CD4+ TCC from patients with AIDS showed enhanced helper function for IgG synthesis in vitro in both autologous and normal allogeneic B cells in comparison to clonable CD4+ T cells of normal donors. Such activity was further potentiated by addition to the cell cultures of anti‐CD3 monoclonal antibody. The majority of CD4+ T cell clones from AIDS patients showed a reduced ability to produce interleukin 2 and interferon‐γ in response to activation with phytohemagglutinin. However, most of them released greater amounts of soluble factor(s) able to promote B cell proliferation of anti‐IgM‐activated normal B cells and to induce the differentiation of normal B lymphocytes into IgG‐secreting cells.

These data demonstrate that most surviving CD4+ T cells in PB of patients with AIDS belong to a T cell subset producing B cell growth and differentiation factors, which may contribute to the B cell hyperactivation seen in AIDS patients.
T lymphocyte recognition of acetylcholine receptor: Localization of the full T cell recognition profile on the extracellular part of the α chain of Torpedo californica acetylcholine receptor
Authors: Yokoi Tsuyoshi , Mulac‐Jeričević Biserka , Kurisaki Jun‐Ichi , Atassi M. Zouhair
Published: March 2007

A series of eighteen consecutive overlapping synthetic peptides, of uniform size and overlaps, which encompass the entire extracellular part (residues 1–210) of the Torpedo californica acetylcholine receptor α chain were examined in vitro for their ability to stimulate lymph node cells from acetylcholine receptor‐primed C57BL/6 (H‐2b), C3H/He (H‐2k), SWR (H‐2q) and SJL (H‐2s) mice. The recognition sites (T sites) by acetylcholine receptor‐primed lymph node cells from these mouse strains resided within six regions on the extracellular part of the α chain. Three of the regions recognized by T cells conincided with regions recognized by antibodies (i.e. B cells) and one of these three regions also coincided with an a‐neurotoxin‐binding region. It is noteworthy that, in addition to sites recognized by both T and B cells, the protein has at least two sites which are recognized exclusively by T cells and to which no detectable antibody responses are directed.
Suppressive effects of C3b on monocyte‐dependent T cell proliferation
Authors: Däubener Walter , Faßbender Birgit , Meuer Stefan , Bitter‐Suermann Dieter , Hadding Ulrich
Published: March 2007

The effect of C3b treatment of human monocytes on secondary antigen‐dependent T cell response was studied. When antigen‐specific T cell blasts were cultivated together with C3b‐treated monocytes the proliferative response was inhibited in a dose‐dependent fashion. This suppressive effect was specific for C3b because heat‐inactivated C3b or buffer alone had no influence on T cell proliferation. In part, this suppressive effect is mediated through a C3b‐induced decreased expression of class II antigens on the surface of treated monocytes, but another suppressive mechanism exists because the C3b pretreatment of monocytes also led to an inhibition of the proliferative response in a class II antigen‐independent T cell proliferation system. In addition to the C3b data, our finding that treatment of monocytes with C3d resulted in a lower T cell proliferation, while C3c has no effect, suggested that C3d, which could be generated from C3b in the culture, may induce the second inhibitory mechanism.
The role of dipeptidyl peptidase IV in human T lymphocyte activation. Inhibitors and antibodies against dipeptidyl peptidase IV suppress lymphocyte proliferation and immunoglobulin synthesis in vitro
Authors: Schön Ekkehard , Jahn Sigbert , Kiessig Stephan T. , Demuth Hans‐Ulrich , Neubert Klaus , Barth Alfred , von Baehr Rüdiger , Ansorge Siegfried
Published: March 2007

Dipeptidyl peptidase IV (DP IV), an ectoenzyme in the cell membrane of T lymphocytes, is an important constituent in the process of lymphocyte activation. This conclusion is drawn from the following observations: (a) Proliferation of peripheral blood lymphocytes induced by mitogenic lectins (phytohemagglutinin, concanavalin A, pokeweed mitogen) is suppressed in the presence of DP IV inhibitors. This effect is specific and applies to an irreversible suicide inhibitor as well as to a competitive one in a dose‐dependent fashion. (b) Inhibition of DNA synthesis was also induced by a polyclonal anti‐DP IV immunoglobulin. (c) As a consequence of impaired T cell function the production of immunoglobulins by pokeweed mitogen‐stimulated lymphocytes is also markedly reduced in the presence of DP IV inhibitors.
Molecular analysis of the antigen receptor of virus‐specific cytotoxic T cells and identification of a new Vα family
Authors: Pircher Hanspeter , Michalopoulos E. Effie , Iwamoto Aichiki , Ohashi Pamela S. , Baenziger Jurg , Hengartner Hans , Zinkernagel Rolf M. , Mak Tak W.
Published: March 2007

We have determined the primary structure of the α/β‐antigen receptor of a lymphocytic choriomeningitis virus (LCMV)‐specific cytotoxic T cell clone (P14). The β chain of the T cell receptor is composed of Vβ8.1, Dβ and Jβ2.4 gene segments while the α chain uses a member of the Vα2 family and Jα TA31. Southern blot analysis of a panel of six other independent LCMV‐specific cytotoxic T cell clones did not reveal any preferential usage of the Vα2 or Vβ8 gene families in the cytotoxic LCMV response. Additionally, we have isolated and sequenced cDNA clones derived from the non‐functionally rearranged α allele of P14. This transcript is composed of a unique Vα gene segment which belongs to a new Vα gene family.
Resistance of mouse cytolytic cells to pore‐forming protein‐mediated cytolysis
Authors: Shinkai Yo , Ishikawa Hitoshi , Hattori Masakazu , Okuimira Ko
Published: March 2007

Pore‐forming protein (perforin, PFP) was isolated from a mouse large granular lymphocyte (LGL) [natural killer (NK‐like)] cell line. Purified PFP lysed a variety of mouse tumor cell lines and helper T lymphocyte cell lines. However, LGL and cytotoxic T lymphocyte cell lines were resistant to PFP‐mediated cell lysis. The presence of hemolytic activity in the granule was examined in these resistant cell lines. Four out of five of these resistant cell lines had hemolytically active granules. We determined whether NK cells freshly isolated from BALB/c nude mouse spleens were resistant to PFP‐mediated cytolysis. Nylon column‐passed spleen cells with an enriched content of NK cells exhibited more resistance than whole spleen cells. Moreover, when spleen cells were treated with PFP the remaining live cells showed enriched NK activity suggesting that normal peripheral cells with NK activity are resistant to PFP. These results indicate that cytolytic cells containing PFP have developed defense mechanisms to inhibit PEP‐mediated cell lysis.
Human immune response to allergens of house dust mite, Dermatophagoides pteronyssinus. III. Cross‐reactivity of bystander idiotopes on allergen‐specific IgE antibodies
Authors: Saint‐Remy Jean‐Marie R. , Lebecque Serge J. , Lebrun Philippe M.
Published: March 2007

Rabbits were inoculated with affinity‐purified human antibodies to the common house dust mite Dermatophagoides pteronyssinus (DPT) to produce anti‐idiotypic (Id) antibodies. The Id carried by human IgE antibodies were studied in a radio‐immunoassay in which specific anti‐DPT IgE were first insolubilized on rabbit F(ab′)2 fragments against human Fcϵ.

In a single individual specific anti‐DPT IgE antibodies shared bystander idiotopes (i.e. idiotopes located outside the antigen‐binding site) with IgG antibodies of the same specificity, since the adsorption on insolubilized anti‐DPT IgG almost completely eliminated the binding of anti‐Id antibodies to IgE. This differed from our previous observations (J.M. R. Saint‐Remy et al., Eur. J. Immunol. 1986. 16: 575) wherein distinct paratope‐associated idiotopes were identified on IgG and IgE anti‐DPT antibodies.

The frequency of cross‐reactions between idiotopes of anti‐DPT IgE antibodies observed in ten unrelated individuals was less than 10% for bystander idiotopes. This finding confirmed the private character of the above idiotopes that we found earlier on anti‐DPT IgG antibodies. However, one anti‐Id antibody preparation was found to react with bystander idiotopes of anti‐DPT IgE of most individuals, thereby suggesting the existence of a recurrent idiotope. The low frequency of inter‐individual bystander idiotope cross‐reactivity contrasted with the public character of paratope‐associated idiotopes.
CDS and CD21 molecules are a functional unit in the cell/substrate adhesion of B‐chronic lymphocytic leukemia cells
Authors: Bergui Luciana , Tesio Luisa , Schena Marina , Riva Margherita , Malavasi Fabio , Schulz Thomas , Marchisio Pier Carlo , Caligaris‐Cappio Federico
Published: March 2007

The modulation of surface molecules on B‐chronic lymphocytic leukemia (B‐CLL) cells was studied in vitro by incubation with CD19, CD20, CD21, CD5 and anti‐IgM antibodies. The cytoplasmic changes were evaluated by analyzing the organization of cytoskeletal F‐actin and the adhesive properties of stimulated B‐CLL cells. The following observations were made: (a) CD5 antigen is capped on the surface of B‐CLL cells (but not on normal CD5+ B and T lymphocytes), (b) On B‐CLL cells, CD5 and CD21, the receptors for the C3d fraction of complement, co‐cap and co‐modulate while surface IgM as well as CD19 and CD20 do not cap. (c) B‐CLL cells, after capping of CD5 or CD21 surface molecules, fail to organize F‐actin into podosomes. (d) The pre‐incubation of B‐CLL cells with either CD5 or CD21 antibodies prevents their binding to purified C3d protein used to coat coverslips. These data indicate that an intimate spatial relationship exists between CD5 and CD21 molecules on the B‐CLL surface. The CD5‐CD21 complex is involved in the redistribution of cytoskeletal proteins which may control the adhesive properties of these malignant B cells.
Human antibody responses to Schistosoma mansoni: the influence of epitopes shared between different life‐cycle stages on the response to the schistosomulum
Authors: Dunne David W. , Grabowska Anna M. , Fulford Anthony J. C. , Butterworth Anthony E. , Sturrock Robert F. , Koech Davy , Ouma John H.
Published: March 2007

Sera from 120 Kenyan schoolchildren who were infected with S. mansoni were individually examined, using an enzyme‐linked immunoabsorbent assay (ELISA), for the presence of IgG and IgM antibodies reactive with antigens derived from adult worms, the outer membrane of the schistosomulum or from the parasite egg. In addition, antibodies against more purified egg antigens, an egg stage‐specific glycoprotein preparation and a polysaccharide egg antigen known to share epitopes with the schistosomular surface were measured in ELISA, as were antibodies reactive with trichloroacetic acid‐soluble and periodate‐insensitive antigens derived from the outer membrane of schistosomulum and antigens shed when schistosomula were cultured in vitro. IgG subclass responses to the unfractionated egg antigen were also measured. The results from each of these assays were compared with the results of each other assay and with the number of parasite eggs excreted by each child, using Spearmans rank correlations.

These comparisons revealed a number of statistically significant positive correlations. IgG4 anti‐egg antibodies correlated better with intensity of infection than did other IgG subclasses. Total IgG responses against polysaccharide antigens did not correlate with intensity of infection as well as IgG responses against other antigens; epitopes shared between the schistosomulum surface and the adult worm were different to those shared with the parasite egg; and, there was antigen‐directed restriction of IgG subclass responses to some egg and adult worm antigens which carried these shared epitopes. It is argued that this might have a qualitative effect on the nature of the antibodies directed against the schistosomulum by infected individuals and therefore have important consequences for the outcome of a subsequent exposure to infection with the same parasite.
Differential expression and interferon response of HLA class I genes in thymocyte lines and response variants
Authors: Girdlestone John , Milstein Cesar
Published: March 2007

cDNA clones which seem to represent the alleles of HLA‐A and ‐B expressed by the thymoma MOLT‐4 have been isolated and used as locus‐specific probes to measure the corresponding mRNA levels in MOLT‐4 and other human thymocyte lines, and the effect of interferon (IFN)−α and −γ on these levels. It is shown in MOLT‐4, and in its derived line YHHH, that HLA‐B mRNA levels are undetectable before treatment but respond to IFN‐α and −γ more markedly than those of HLA‐A. This differential induction is best shown with YHHH, which is hypersensitive to IFN‐α, where the HLA‐B mRNA levels increase to a level threefold those of HLA‐A. Other thymocyte lines tested also showed preferential induction by IFN‐α of HLA‐B, although the basal levels of HLA‐A and ‐B tended to be similar. The effect of the altered ratio of HLA‐A to ‐B mRNA on surface expression of the antigens and the correlation between basal level expression and inducibility are discussed.
Isolation of antigen‐specific T cell clones from nonresponder mice
Authors: Abromson‐Leeman Sara , Laning Joseph , Cantor Harvey , Dorf Martin E.
Published: March 2007

The mechanisms responsible for major histocompatibility complex (MHC)‐linked unresponsiveness are still poorly understood. Here we examine the cellular events that follow when B10.A mice are immunized with cow insulin, an antigen to which they make no apparent immunologic response. Despite the fact that there is no detectable antibody or T cell proliferative response to cow insulin, we have been able to clone out responding T cells after priming and restimulating in vitro with this “nonimmunogenic” antigen. These cells are L3T4+, and co‐recognize specific antigen and class II MHC gene products. The data demonstrate that “nonresponder” mice to cow insulin have both the capacity to present antigen and T cells capable of recognizing that antigen. The diversity within this population was investigated by analyzing various parameters of cellular activation. These include fine specificity of both antigen and MHC recognition, as well as recognition of allogeneic MHC and Mls determinants. In addition, the antigen‐presenting cell requirements were studied. The results demonstrate that this population comprise a surprisingly heterogeneous group in terms of its repertoire of receptors.
Immunoglobulin gene expression is a normal differentiation event in embryonic thymocytes
Authors: Gallagher Pauline F. , Miller Jacques F. A. P.
Published: March 2007

By in situ hybridization to frozen sections of mouse embryos, we have localized cells transcribing the Ig Cμ, gene during ontogeny. Transcripts were detected from before day 14 of gestation in individual pre‐B cells in the liver and, surprisingly, in a large proportion of thymocytes between days 15 and 18. The level of μ RNA sequences in the thymus at day 17 was much higher than has been observed for adult thymocytes; from grain counts, the amount of μ RNA was similar to that observed for Ti γ RNA. These findings suggest that Ig and Ti genes are under similar transcriptional controls during Ti gene recombination and that elevated μ RNA production is a normal event early in the intrathymic differentiation of T cells.
Memory B cells in T cell‐dependent antibody responses colonize the splenic marginal zones
Authors: Liu Yong‐Jun , Oldfield Susan , Maclennan Ian C. M.
Published: March 2007

Specific hapten‐binding B cells were identified in the splenic marginal zones following immunization with hapten‐protein conjugates. Hapten binding by marginal zone B cells does not appear to be due to passive absorption of anti‐hapten antibody. For double immunization with two haptens, 2,4‐dinitrophenyl (DNP) and 2‐phenylox‐azalone (Ox) each conjugated to hemocyanin, resulting in the appearance of discrete DNP‐binding cells and Ox‐binding cells in the marginal zone. Very few cells were identified which bound both haptens. The hapten‐binding cells in the marginal zones have a phenotype characteristic of other marginal zone B cells. They express surface IgM but not IgD. Occasional cells also have surface IgG2C. All hapten‐binding cells possessed the antigen recognized by the monoclonal antibody HIS 14 but lacked those identified by HIS 24 and HIS 22. Hapten‐binding B cells were shown to have been in cell cycle shortly before entering the marginal zone but were no longer in cell cycle after arriving at that site. Once in the marginal zone hapten‐binding cells were shown to remain in that site for upwards of 2 weeks. Following reimmunization with DNP‐hemocyanin, DNP‐binding but not Ox‐binding cells were lost from the marginal zone. At the same time DNP‐binding cells arrived in the periarteriolar lymphocytic sheath and to a lesser extent the follicles. These cells were in active cycle and appeared to give rise both to plasma cells and marginal zone hapten‐binding cells. It is concluded that hapten‐binding cells found in the marginal zones are memory B cells i.e. they have been derived from B cells which have undergone antigen‐driven proliferation, they are no longer in cell cycle but can be induced to re‐enter cell cycle by subsequent exposure to antigen.

Good antibody responses were obtained following immunization with hapten‐polysaccharides; however, no hapten‐binding cells appeared in the marginal zones in response to these T cell‐independent type 2 antigens.
A significant proportion of normal resting B cells are induced to secrete immunoglobulin through contact with anti‐receptor antibody‐activated helper T cells in clonal cultures
Authors: Riedel Catherine , Owens Trevor , Nossal Gustav J. V.
Published: March 2007

This report describes single‐cell techniques to address the nature of a cellular interaction in which activated T lymphocytes stimulate small resting B cells to develop into antibody‐forming cell clones in the absence of any surface immunoglobulin ligand or an antigen bridge. The cloned T helper cell line E9.D4 was stimulated with the anti‐Vβ8 antibody F23.1 bound to the plastic of Terasaki 10‐γl culture wells. When an excess of T helper lymphocytes was used (1000 X‐irradiated or 600 unirradiated, stimulated E9.D4 cells), 10‐25% of B cells responded by antibody formation as judged by an enzyme‐linked immunosorbent assay performed after 5 days of culture. When one or a very small number of B cells were present, the rate‐limiting step to antibody‐forming cell formation was the number of T cells present. Far fewer T cells sufficed for stimulation when culture trays were tilted to force T and B cells into proximity at the sulcus formed at the bottom edge of the culture wells. When T cell numbers were limiting, unirradiated T cells out‐performed irradiated T cells. Some cell clones held for 7 days switched to IgG antibody production.

E9.D4 supernatants were virtually ineffective in causing B cell stimulation, even when 3T3 filler cells were added to support cultures. The results suggest that cell contact, and perhaps conjugate formation, with a strongly activated T cell can cause changes in the adjacent resting B cells akin to those of Ig receptor cross‐linking, following which a lymphokine flux (even one not involving IL4 and 5) promotes antibody‐forming cell development.
Immunoregulatory functions of paf‐acether II. Decrease of CD2 and CD3 antigen expression
Authors: Vivier Eric , Salem Patrick , Dulioust Anne , Praseuth Daniele , Metezeau Philippe , Benveniste Jacques , Thomas YolèNe
Published: March 2007

Paf‐acether (platelet‐activating factor) is a phospholipid initially described as a potent platelet‐aggregating compound. It is produced by numerous cell types and is now considered as an important mediator of cell‐cell interactions. The effect of paf‐acether on the expression of CD2 and CD3, two human T cell surface glycoproteins, was investigated by indirect immunofluorescence and flow cytometry. Paf‐acether partially down‐regulated, in a time‐ and dose‐dependent manner, CD2 and CD3 but not HLA class I antigen expression on peripheral human T cells and Jurkat cells. Lysophosphatidylcholine, a phospholipid closely related to paf‐acether, had no detectable modulatory effect on CD2 and CD3 expression. In addition to CD2/CD3 modulation, pafacether markedly inhibited T cell proliferative response not only to phytohemagglutinin or concanavalin A but also to anti‐CD3 or a stimulatory combination of anti‐CD2 monoclonal antibodies. These data demonstrate for the first time that lipid mediators such as paf‐acether might be involved in the regulation of the expression of cell surface glycoproteins that are essential in the execution of T cell function.
induction of human in vitro ige synthesis via stimulation by anti‐cd3 antibody
Authors: Yang Xiao‐Dong , Weck Alain L. De , Stadler Beda M.
Published: March 2007

Mitogens such as pokeweed mitogen, Staphylococcus aureus Cowan I, con‐canavalin A and phytohemagglutinin and monoclonal anti‐CD antibodies were examined for their‐ capacity to induce IgE synthesis by peripheral blood leukocytes obtained from both atopic and nonatopic individuals. While lectins failed to induce IgE synthesis, monoclonal anti‐CD3 antibodies were very potent stimuli for the induction of human in vitro IgE synthesis, possibly due to the activation of T cells. Activation via CD4 or CD8 molecules by OKT4 or OKT8 antibodies did not lead to a T cell‐dependent modulation of IgE synthesis. PWM acted in synergy with the enhancing effect of anti‐CD3 antibodies for IgE synthesis. In vitro IgG production was less affected. These results indicate that activation of T cell via CD3 molecules may be important in the regulation of IgE immune responses in man. Furthermore, the successful induction of IgE synthesis by anti‐CD3 antibody in unfractionated peripheral blood leukocytes culture provides a simple model for investigation of human IgE regulatory mechanism in vitro.
Anti‐suppressor effect of cyclophosphamide on the development of spontaneous diabetes in nod mice
Authors: Yasunami Reiko , Bach Jean‐FrançOis
Published: March 2007

In the NOD mouse, an autoimmune process beginning by 5 weeks of age with lymphocyte infiltration and destruction of insulin‐secreting beta cells leads to overt diabetes which begins to appear by 11 weeks of age. Although there is a high incidence of insulitis by 10 weeks of age (> 80%) in both males and females, by 30 weeks of age diabetic symptoms have occurred in 53‐80% of females and in 1240% of males. Intraperitoneal injection of a high dose (200 mg/kg) of cyclophosphamide (CY) consistently induces the onset of diabetes in male and female NOD mice at an age when spontaneous diabetes rarely occurs. Spleen T cells from CY‐induced diabetic mice are capable of transferring the disease into irradiated nondiabetic syngeneic recipients. This indicates that the diabetogenic effect of CY is not mediated by direct toxicity on pancreatic beta cells but is mediated by abrogation of a suppressor mechanism which may prevent activation of T cells responsible for the development of diabetes in the NOD mouse. Additionally, CY is only effective in NOD mice and not in F1 hybrids between NOD and other strains of mice. Thus, the potential beta cell aggressor mechanism is not present in these hybrids as it is in homozygous mice, which indicates that it is not under the control of dominant genes.
In vivo function of natural killer cells as regulators of myeloid precursor cells in the spleen
Authors: Hansson Mona , Petersson Max , Koo Gloria C. , Wigzell Hans , Kiessling Rolf
Published: March 2007

In order to study the in vivo effect that natural killer (NK) cells may have on hematopoietic precursor cells in the autologous host, NK‐depleted mice were constructed by injection of an anti‐NK‐1.1 monoclonal antibody. Only the spleen, and not the bone marrow, of such NK‐depleted mice shows an increase in the number of myeloid precursur cells able to form colonies in soft agar as compared to control mice with normal levels of NK activity. The increase in number of hematopoietic immature cells due to lack of a regulatory cell (i.e. NK cell) is selective for the committed myeloid precursur cells, and not evident for erythroid or pluripotent progenitor cells. This is direct evidence in support of the hypothesis that NK cells in the autologous host serve as a regulator of extramedullary myelopoiesis.
The role of protein kinase C in early activation vs. growth of T lymphocytes
Authors: Friedrich Bengt , Gullberg Martin
Published: March 2007

Protein kinase C (PKC) has been implicated in the signaling of a number of cellular responses including activation of T cells. In an approach to study the role of PKC in both early activation and interleukin 2 (IL2)‐dependent growth, we have used in vivo phosphorylation of endogenous substrates as a marker for PKC activation. In the present report the requirements for CD3‐specific activation of PKC are defined, and it is shown that the conditions required for optimal activation coincide with the induction of a proliferative response. Moreover, it is also shown that IL2 receptor interactions induce only low levels of PKC substrate phosphorylation and that IL2 does not cooperate with CD3‐specific signals on the level of PKC activation.
Long‐term depletion of cd8+ t cells in vivo in the rat: no observed role for cd8+ (cytotoxic/suppressor) cells in the immunoregulation of experimental allergic encephalomyelitis
Authors: Sedgwick Jonathon D.
Published: March 2007

A method is described for the long‐term depletion of CD8+ T cells in the rat. Employing Lewis rats depleted of this cell type it is shown that such animals acquire, and subsequently recover from both passively and actively induced experimental allergic encephalomyelitis (EAE) in a comparable fashion to normal animals. Furthermore, after spontaneous recovery from the initial bout of disease, CD8+ T cell‐depleted rats do not show any signs of relapse and, like normal rats following recovery from active EAE, are still resistant to further attempts at disease induction. Overall, these data do not support a role for the classic cytotoxic/suppressor (CD8+) T cell in the immunoregulation of EAE in the Lewis rat.
Interferon‐γ is not an antiviral, but a growth‐promoting factor for t lymphocytes
Authors: Landolfo Santo , Gariglio Marisa , Gribaudo Giorgio , Jemma Cristina , Giovarelli Mirella , Cavallo Giorgio
Published: March 2007

The effects of interferon (1FN)‐γ or IFN‐α/β on virus yield, (2′‐5′)oligo(A) synthetase activation, H‐2 antigen expression and proliferation of T lymphocytes have been investigated. Under the culture conditions used, vesicular stomatitis virus or Semliki Forest virus replication in T cells was not impaired by the addition of IFN‐γ, whereas it was completely inhibited by the addition of IFN‐α/β. In contrast, B cell lines, macrophage‐transformed cell lines and fibroblasts were fully protected by both IFN‐γ as well as IFN‐α/β following virus infection. The lack of sensitivity of T lymphocytes to the antiviral effects of IFN‐γ was not due to absence of specific membrane receptors, since in saturation binding experiments with 125I‐labeled murine IFN‐γ most T cell lines displayed a number of binding sites and a degree of affinity comparable to those found on B cells, which are fully sensitive to IFN‐γ antiviral activity. Analysis of IFN‐induced dsRNA‐dependent (2′‐5′)oligo(A) synthetase activity, one of the biochemical markers for cellular responses to IFN, showed that it was not induced in T lymphocytes after IFN‐γ treatment, whereas IFN‐α/β induced high levels. Both IFN‐γ and IFN‐α/β enhanced H‐2 antigen expression on T cells as well as on cells of different histological type. Moreover, when IFN‐γ was tested for its antiproliferative activity on T cells, it was found to consistently potentiate the response of these cells to mitogens or growth factors, rather than inhibit their proliferation. Taken as a whole these results suggest that on T lymphocytes IFN‐γ should not be regarded as an antiviral agent, but rather as a modulator of T cell growth and functional differentiation, transducing intracellular signals dissimilar to those observed with target cells of different origin.
An acquired immune suppression in mice caused by infection with lymphocytic choriomeningitis virus
Authors: Roost Hanspeter , Charan Shiv , Gobet Rita , Rüedi Edith , Hengartner Hans , And Alana Althage , Zinkernagel Rolf M.
Published: March 2007

A murine model of virally induced acquired immunodeficiency was analyzed in mice. The effect of systemic infection with various isolates of lymphocytic choriomeningitis virus (LCMV) on the capacity of mice to mount a T cell‐independent IgM and a T cell‐dependent IgG neutralizing antibody response against a subsequent infection with vesicular stomatitis virus (VSV) was analyzed. DBA/2 mice infected with the LCMV‐WE isolate were impaired in their IgM and IgG responses to VSV. Immune suppression was not caused by interferons inhibiting proper VSV antigen expression, since responses to inactivated VSV were also suppressed. The higher the dose of the LCMV and the lower the dose of the challenging VSV infection the more drastic was the apparent lack of immune responsiveness and the longer it lasted. Kinetics of induction of suppression of the T cell‐independent IgM responses closely followed that of a normal cytotoxic T cell response to LCMV‐WE, starting on day 6 and reaching maximal levels by day 8 to 10. The T cell‐dependent IgG response to VSV was suppressed with a kinetics that was shifted by about 6 days when compared with suppression of IgM responses, i.e. LCMV infection on the same day or before (but not after) VSV infection led to suppression of IgG responses that are usually first detected by day 6‐7 after initiation of the VSV infection. Severity and duration of immunosuppressiveness depended upon the LCMV isolate and the mouse strain used: LCMV‐WE and LCMV‐Docile were most, whereas LCMV‐Armstrong was in general least immunosuppressive. Antibody responses to VSV‐NJ seemed to be more subject to LCMV‐induced immune suppression than VSV‐IND‐specific responses. Mouse strains differed considerably with respect to extent of suppression, dependent upon both major histocompatibility genes (MHC) and non‐MHC genes. DBA and Swiss type mice were generally more susceptible than C57BL and CBA mice, and H‐2q and H‐2k seemed to be more susceptible than H‐2b or H‐2d mice.

Mice infected with LCMV‐WE showed signs of acquired immunodeficiency diseases since they were more susceptible to superinfection with VSV and developed paralytic disease and tended to die from VSV infection. Since LCMV is basically a noneytopathic virus, this murine model of virally induced immune suppression may serve to analyze immune pathogenesis of virus‐induced acquired immunodeficiency.
Signal transduction through cd4 receptors: stimulatory vs. inhibitory activity is regulated by cd4 proximity to the cd31t cell receptor
Authors: Ledbetter Jeffrey A. , June Carl H. , Rabinovitch Peter S. , Grossmann Angelika , Tsu Theta T. , Imboden John B.
Published: March 2007

The binding of antibody to the CD4 molecule inhibits mobilization of cytoplasmic free calcium ([Ca2+]i) in response to CD3 cross‐linking on resting T cells. Similarly, when CD3 and CD4 are independently and simultaneously cross‐linked, calcium mobilization is inhibited when compared to that induced by cross‐linking CD3 alone. In contrast, when anti‐CD4 and anti‐CD3 are cross‐linked together, calcium mobilization is substantially higher than from CD3 cross‐linking alone. A heteroconjugate consisting of covalently bound CD3 and CD4 monoclonal antibodies (mAb) retains the ability to mobilize [Ca2+]i in CD4 cells at protein concentrations approximately two orders of magnitude lower than the free CD3 mAb, and the activity of the heteroconjugate is inhibitable by free CD4 mAb. The CD3/CD4 heteroconjugate also shows significantly greater activity in stimulation of inositol phosphate IP1, IP2 and IP3 synthesis in T cells than the CD3 mAb alone, and again the activity is inhibited by free CD4 mAb. The activity of the CD3/CD4 heteroconjugate is not simply due to oligomerization, since CD3/CD3 or CD4/CD4 homoconjugates or homoconjugate mixtures did not show increased activity. Other heteroconjugates (CD3/CD5 and CD3/CD28) were not different than the CD3/CD3 homoconjugate in their ability to increase [Ca2+]i. Purified CD4 T cells that do not respond to CD3 mAb in solution do respond to the CD3/CD4 heteroconjugate in solution by proliferating in the presence of a CD28 mAb, with a significant fraction of CD4 cells entering the second cycle within the first three days of stimulation. The CD3/CD4 heteroconjugate co‐modulates the CD3 and CD4 receptors, indicating that the heteroconjugate is not simply anchoring the T cell receptor to the T cell surface like anti‐CD3 on a solid surface. These results suggest that CD4 plays an active role in signal transduction when brought into close physical proximity to the CD3/T cell receptor complex during major histocompatibility complex class II‐restricted antigen presentation.
Characterization and functional properties of a novel monoclonal antibody which identifies a T cell receptor in chickens
Authors: Cihak Josef , Ziegler‐Heitbrock H. W. LöMs , Trainer Hans , Merkenschlager Michael , Lösch Uli
Published: March 2007

A monoclonal antibody, mAb6, was produced that specifically bound to chicken T lymphocytes. Immunofluorescence analysis using a fluorescence‐activated cell sorter revealed that the antibody reacted with approximately 50% of blood lymphocytes and with approximately 40% of splenocytes and thymocytes. It did not react with bursa1 cells and erythrocytes. Among different types of hemopoietic cell lines, only a T cell line was reactive with mAb6. When coupled to Sepharose 4B beads, mAb6 was found to be highly mitogenic for chicken T cells. In soluble form, mAb6 inhibited concanavalin A‐induced T cell proliferation and the cytotoxic activity of allosensitized T cells, the inhibition occurring in a dose‐dependent manner for both assays. Thus, the tissue distribution and the effects of this antibody on T cell responses suggest that mAb6 recognizes a T cell receptor present on a large proportion of chicken T cells.
Differential expression of two t cell receptors, tcr1 and tcr2, on chicken lymphocytes
Authors: Chen Chen‐Io H. , Cihak Josef , Lösch Uli , Cooper Max D.
Published: March 2007

A monoclonal antibody, TcR2, has been shown to recognize an avian homologue of the mammalian α/β T cell receptor (TcR). The TcR2‐reactive molecule was found to be a T3‐associated heterodimer with relative molecular mass of 90‐kDa consisting of disulfide‐linked 50‐kDa and 40‐kDa polypeptides. The sizes of the deglycosylated TcR2 polypeptides differed from those of TcR1, an avian homologue of the mammalian γ/δ T cell receptor. Immunofluorescence analysis revealed that TcR1 and TcR2 are expressed on separate populations of T cells during their development first in the thymus and then in the periphery. Ontogenetic studies revealed that the TcR1+ thymocytes are generated first and the generation of TcR2+ cells begins approximately 3 days later. While most TcR2+ cells in the thymus expressed both CT4 and CT8, TcR2+ cells in blood and the spleen were either CT4+ or CT8+. The TcR1+ cells in blood and thymus were CT4−CT8−, but the majority of TcR1+ cells in the spleen surprisingly expressed the CT8 marker. The data suggest that TcR1 and TcR2 cells are generated in the thymus as separate T cell sublineages.
Class‐specific suppression of human b cell maturation by iga‐binding factors
Authors: Millet Isabelle , Samarut Christiane , Revillard Jean‐Pierre
Published: March 2007

IgA‐binding factors (IgA‐BFs) were prepared by chromatography on Sepharose 4B beads covalently linked to dimeric and polymeric monoclonal IgA1 from supernatants of peripheral blood mononuclear lymphocytes (PBMC) and human B cell lines incubated in serum‐free medium. Receptors for IgA, as revealed by the binding of biotinylated monoclonal IgA1, were expressed on monocytes, T‐enriched and T‐depleted lymphocytes. IgA‐BFs or control eluates were added to pokeweed mitogen (PWM)‐stimulated PBMC cultures, and their effects on the terminal differentiation of polyclonally activated human B cells were assessed by enumeration of intracytoplasmic IgM‐, IgG‐ or IgA‐containing cells. A selective decrease of IgA‐containing cells was observed in the presence of IgA‐BFs whereas IgM‐ and IgG‐containing cells remained unchanged. Differential counts of B blasts and plasma cells revealed that only the former were decreased following addition of IgA‐BFs. Kinetic studies indicated that maximum inhibition of IgA‐containing cell generation was achieved when IgA‐BFs were added during the first 5 days of PWM‐stimulated PBMC cultures, whereas no inhibition could be demonstrated when IgA‐BFs were added 24 h before harvesting. IgA‐BFs did not decrease [3H]thymidine incorporation in PWM‐stimulated PBMC cultures. They diminished the proliferation of the surface IgA+ monoclonal human B cell line DAKIKI, but not that of the surface IgA− IM‐9 cell line. Several control eluates obtained from the same cell supernatants absorbed on Sepharose 4B, Sepharose 4B‐IgG or Sepharose 4B‐β2‐microglobulin had no effect. Finally, IgA‐BFs prepared from supernatants of two human B cell lines bearing receptors for IgA selectively depressed the generation of intracytoplasmic IgA+ cells in PBMC cultures stimulated by PWM. Altogether the data indicate that IgA‐BFs obtained by spontaneous release from heterogeneous mononuclear cell suspensions or from IgA receptor‐positive human monoclonal B cell lines selectively depress the maturation of B cells into IgA plasma cells and the proliferation of a surface IgA+ B cell line.
The effect of immunization with a 14‐kda streptococcal antigen on primate t cell and b cell responses
Authors: Fellowes Raymond , Fortune Farida , Bergmeier Lesley A. , Lehner Thomas
Published: March 2007

A streptococcal antigen (SA) of 185 kDa was isolated from Streptococcus mutuns and this antigen induced in vitro helper, suppressor and contrasuppressor activities with primate peripheral blood lymphocytes. The 185‐kDa SA was then treated by sodium dodecyl sulfate and yielded a 4‐kDa SA which was capable of eliciting only helper activity. We have now cleaved the 185‐kDa SA with cyanogen bromide, in an attempt to identify suppressor and contrasuppressor determinants. A 14‐kDa SA was separated from the cyanogen bromide digest and its ability to elicit T cell and B cell functional activities was tested in rhesus monkeys. Whereas the 185‐kDa SA (and 4‐kDa SA) elicited high serum anti‐SA antibodies and the CD4 cells showed an increase in DNA synthesis, this was not demonstrable with the 14‐kDa SA. However, the 14‐kDa SA, unlike the 185‐kDa SA, activated a significant proportion of CD4 and CD8 cells to bind the Viciu villosu lectin (VV) and this is a characteristic feature of contrasuppressor cells. We then studied the effect of sequential immunization of monkeys with the 14‐kDa SA, followed by the 185‐kDa SA. The results of this showed suppression of the CD4 proliferative response, in the presence of a normal antibody production. We suggest that the split tolerance between the T cell proliferative and B cell differentiating functions might be interpreted on the basis of suppressor CD8 cells inhibiting the CD4 proliferative phase and the W‐adherent CD8 cells contrasuppres‐sing B cell antibody formation.
Ontogeny of human complement receptors cr1 and cr3: expression of these molecules on monocytes and neutrophils from maternal, newborn and fetal samples
Authors: Adinolfi Matteo , Cheetham Mark , Lee Tak , Rodin Adam
Published: March 2007

Higher levels of the expression of CR1 and CR3 molecules were detected on the surface of monocytes and neutrophils from maternal and newborn (cord) blood samples than in adult controls. Chemotactic factors such as formyl‐methionyl‐leucylphenylalanine or leukotriene B4 induced an increase of the expression of CR1 and CR3 which was more pronounced on cells from maternal and cord samples than from nonpregnant adult controls. CR1 and CR3 molecules were detected in monocytes and neutrophils from peripheral blood obtained from fetuses more than 14 weeks old and on subpopulations of cells in bone marrow, spleen and thymus.
Expression of receptors for iga on mitogen‐stimulated human t lymphocytes
Authors: Millet Isabelle , Panaye Genevikve , Revillard Jean‐Pierre
Published: March 2007

This study demonstrates that activation of human peripheral blood mononuclear cells (PBMC) by the T cell mitogens phytohemagglutinin (PHA) and concanavalin A (Con A) induces the expression of receptors for IgA without addition of IgA to the culture medium. Cells bearing receptors for IgA were determined by indirect immuno‐fluorescence using human secretory IgA and fluoresceinated goat anti‐human IgA or goat anti‐secretory component antibodies. Among freshly isolated PBMC, 4.7 ± 1.7% of T cells, 12.7 ± 12.5% of B cells and 14.4 ± 7.6% of monocytes were found to be IgA receptor positive. In unstimulated PBMC cultures the percentage of IgA receptor‐positive cells slightly increased at 48 h and was more elevated after 7 days. In Con A‐stimulated cultures 24.3 ± 18.5% of the cells expressed receptors for IgA after 48 h. Then, the number decreased and rose again thereafter. PHA stimulation induced an increase of smaller magnitude with similar kinetics. Induction of receptor for IgA on activated T cells was demonstrated by double‐labelling experiments showing more CD8+ than CD4+ cells with receptors for IgA among Con A‐activated PBMC. Furthermore, PHA or Con A stimulation of B cell‐depleted PBMC suspensions resulted in a marked increase of cells bearing receptors for IgA. Expression of these receptors was down‐regulated by recombinant interferon‐γ (250 units/ ml) and by prostaglandin PGE2 (100 nM) both on unstimulated and mitogen‐activated PBMC. The receptor for IgA was distinct from the asialoglycoprotein receptor and did not cross‐react with the poly‐Ig receptor of epithelial cells. It was concluded that, in the absence of inducing exogenous IgA, T cell mitogens trigger the expression of receptors for IgA. Therefore, T cell activation is associated with the down‐regulation of receptors for IgM and the increased expression of receptors for IgG, IgA and IgE.
The human t cell receptor α‐δ locus: a physical map of the variable, joining and constant region genes
Authors: Griesser Henrik , Champagne Erik , Tkachuk Douglas , Takihara Yoshihiro , Lalande Marc , Baillie Eric , Minden Mark , Mak Tak W.
Published: March 2007

In this study a physical macro‐restriction map of the entire human a locus that spans about 1000 kilobase pairs and includes the Vα Jα and Cα genes is presented. Evidence is provided that gene duplications were involved in the increase of genomic diversity of Vα genes. In addition, we show a detailed map of a 40‐kb region located approximately 100 kg upstream of the human Cα gene. Direct evidence is provided to support that the human a chain locus, like the murine, also contains another T cell constant region gene in the a chain locus, the human σ chain gene. In addition, two J segments and one D segment have been identified. Using these genomic probes, we show that several T cell lines, including those known to express the surface γ/σ heterodimer, have rearranged this region. The design of two separate centers of rearrangement within one locus that are involved in rearrangement events at different times, and the presence of high number of J segments in this region, may render the locus highly vulnerable to chromosomal translocation during T cell developement.