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At least 1,333 records · Page 74Linked to original sources
PubMed1994

Immunotherapy of bladder cancer with cytokine gene-modified tumor vaccines.

This study explored the use of cytokine gene-modified tumor cells as cellular vaccines for the treatment of bladder cancer. The mouse MBT-2 tumor is an excellent model for human bladder cancer. This carcinogen-induced tumor of bladder origin resembles human bladder cancer in its etiology and histology and responds to treatment in a manner similar to that of its human counterpart. In a previous study we have shown that interleukin 2 (IL-2)-secreting, irradiated, MBT-2 cell preparations were capable of curing animals from orthotopically established tumors and engendered protective immunological memory in the cured animals. In this study we have compared the effectiveness of several cytokines and found that while IL-1 alpha, IL-1 beta, and gamma-interferon were only weakly effective in the therapeutic vaccination protocol, granulocyte-macrophage colony-stimulating factor was almost as effective as but not superior to IL-2, as reported previously for another tumor model system. Induction of cytotoxic T-lymphocyte correlated only poorly with the therapeutic benefit of the cytokine gene-modified tumor cell preparations, questioning its prognostic value for the development of improved genetically modified tumor vaccines.

Animals↗
PubMed1975

Experimental studies on cholera immunization. 4. The antibody response to formalinized Vibrio cholerae and purified endotoxin with special reference to protective capacity.

The primary and secondary antibody responses in rabbits, intravenously immunized with formalin-killed Vibrio cholerae, were studied with regard to amount, immunoglobulin class distribution and binding qualities of the antibodies to the bacterial endotoxin. Further the protective capacity of antisera and purified antibodies against experimental cholera infection was analyzed and related to the in vitro characteristics of the immune preparations. For the employed 1,000-fold varied range of bacteria used for immunization, the dose dependance of the amount and binding qualities of the antibodies, formed after a single antigen injection, was negligible. In the secondary responses, however, slightly increasing antibody titres and avidities as well as moderately rising protective titres were registered with increasing immunization doses. In the primary response to an optimally immunogenic dose of 1 X 10(10) bacteria the highest IgM titres were noted after 1 week and the maximal IgG titres after 6 weeks, whereas the avidity of vibriocidal antibodies and the protective titres of sera increased for at least 3 months. A booster injection 4 weeks after the primary immunization gave the highest IgG, IgM and protective titres within 1 week, whereafter all titres gradually decreased. Moreover, higher maximal antibody and protective titres were noted in the secondary than in the primary response. An immunological memory could also be induced by purified V. cholerae lipopolysaccharide (LPS), since a booster injection of this antigen gave rise to higher and earlier appearing antibody titres than the first immunization. The influence of the interval between a first and a second immunization on the amount and the avidity of the secondary response antibodies was comparatively small, whereas the protective titres increased markedly with shortening interval. The relation between protection against experimental cholera, as tested in the rabbit small bowel loop system using live vibrios for challenge, and the in vitro estimates of antibody amount and binding properties was poor. However, the IgM antibody titres, determined with an immunosorbent assay, and the antibody binding qualities, as measured by quantitative inhibition in a vibriocidal assay, showed statistically significant correlations with the protective titres. Purification of anti-endotoxin antibodies was achieved by affinity chromatography using columns with V. cholerae LPS covalently coupled to Sepharose beads. The antibodies bound specifically to the gel and could later be eluted by acid buffers. Decreasing pH of the buffer released antibodies with increasing avidity. Antiserum taken early after a primary immunization had a higher proportion of antibodies, eluted at a high pH, than antisera taken late in the primary and secondary responses.

Absorption↗
PubMed1993

Deoxyspergualin. Mode of action and clinical trials.

Corticosteroids are commonly used in combination with cyclosporine in clinical kidney recipients, and administered indefinitely to many patients. Long-term administration of steroids is associated with a number of serious side effects including hypertension, obesity, hyperlipidemia, diabetes mellitus, cataract, osteoporosis, infection, moon face, and so on. A disturbance of growth is also a serious problem in pediatric patients. It is therefore desirable to discontinue the administration of steroid in renal allograft patients. For the withdrawal of steroid, it is quite important to thoroughly inhibit the recipient immune responses during the induction phase of immunosuppression without any serious adverse effect, that the patient may not retain immunological memories against donor antigens for a long period. Thus, we have been performing extensive immunosuppressive therapy using quadruple drugs, that is, DSG, cyclosporine, mizoribine, and prednisolone, during the early stage after kidney transplantation for withdrawal of prednisolone during the maintenance stage. Up to now, 19 recipients were treated with this protocol. In these patients, 8 were completely discontinued on the steroid and have been maintaining excellent graft function 9.2 to 32 months after transplantation, and 2 were reduced on the steroid to 5 mg. The present protocol may contribute greatly toward the quality of life in renal recipients.

Adrenal Cortex Hormones↗
PubMed1993

[Poliomyelitis in The Netherlands, 1979-1991: immunity and exposure].

An overview is presented of serological and virological studies on poliovirus immunization and circulation in the Netherlands, performed between 1979 and 1991. In this period, only three patients with poliomyelitis were notified. All had acquired the infection abroad. The vaccinations in the national immunization programme, using inactivated poliovirus vaccine, build a strong immunity. This can also be seen in age-stratified serological profiles of the Dutch population. In these surveys, persons from the time at which vaccination was offered have neutralizing antibodies. Older persons, especially those born between 1930 and 1945, sometimes lack antibodies. However, 85-90% of them show a rapid booster response upon vaccination, demonstrating immunological memory. Hence, they will be protected against poliomyelitis upon contact with wild poliovirus. Virological data show a regular import of poliovirus, especially in adoptive children tested on entry into the Netherlands, coming from developing countries. Nearly all other virus isolates in Dutchmen were related to import from such countries. None of the imported patients or other persons in whom poliovirus was detected spread the virus over the country. It demonstrates that as a rule the herd immunity of the well-vaccinated Dutch population is good. Exceptions occur, however, as demonstrated by the epidemics in 1978 and 1992. Large socio-geographic clusters of susceptible people who refuse vaccinations are not sufficiently protected.

Antibodies, Viral↗
PubMed1993

The lymphocyte locomotion assay in colon and breast cancer long survivors.

Cell-mediated immunity versus tumour antigens (cytosols) of the same histotype and site was evaluated by means of the lymphocyte locomotion (LL) assay in 46 colorectal adenocarcinoma and 41 breast ductal infiltrating carcinoma patients 36-220 months after surgical resection. Lymphocyte locomotion positivity was observed in 27/46 (58.7%) and 27/41 (65.9%) patients, respectively. These results indicate that a high percentage of long survivors retain an immunologic memory of the tumour antigen to which they have been exposed.

Adenocarcinoma↗
PubMed1996

In vivo cytokine production in murine listeriosis. Evidence for immunoregulation by gamma delta+ T cells.

Differential cytokine production by gamma delta+ T cells influences Th1 and Th2 responses. Here, we describe the in vivo kinetics of peritoneal and splenic gamma delta+, CD4+, and CD8+ T cell cytokine responses during primary and secondary Listeria infections. The data show differences in the kinetics of IFN-gamma-producing alpha beta+ splenocytes consistent with immunologic memory. Most noteworthy, however, was the elevated production of IL-10 by splenic gamma delta+ T cells in the red pulp and marginal zones that coincided with maximal IFN-gamma production and with a decrease in inflammation and tissue damage. This result implies a role for gamma delta+ T cells in the control of Th1 responses.

Animals↗
PubMed1996

Immunotherapy of cancer with genetically modified tumor vaccines.

Distant metastasis is the major cause for therapeutic failures in Clinical oncology. Active immunotherapy in the adjuvant setting of patients with low tumor volume would contribute to further reduction of the remaining tumor and establish long-lasting immunity that could protect the patient from recurrence of disease. Studies employing rodent tumor models with little or no intrinsic immunogenicity have shown that genetically modified tumor cell preparations consisting of irradiated tumor cells transduced with and expressing cytokines, such as interleukin-2 (IL-2), IL-6, interferon-gamma (IFNgamma), or granulocyte-macrophage colony stimulating factor (GM-CSF), or co-stimulatory molecules, such as B7-I, were capable of inducing the regression of preexisting tumors and cure animals from their disease. Moreover, in some instances, the cured animals have retained immunological memory, as indicated by the fact that animals have resisted a second challenge with the parental tumor cells. Induction of potent immune responses in tumor-bearing animals against nonimmunogenic or weakly immunogenic tumors supports the view that active immunization of cancer patients deserves consideration despite lack of demonstrable immunogenicity in many human tumors.

Animals↗
PubMed1996

Lung eosinophilia in response to intravenously injected Trichinella spiralis.

Mice were injected intravenously with killed muscle-stage larvae of the parasitic nematode Trichinella spiralis. This induced eosinophilic lung inflammation, the degree of eosinophilia was detected and measured by broncho-alveolar lavage. Subsequent in vivo restimulation by Trichinella antigens produced an enhanced lung response, showing that exposure to killed larvae generated an effective immunological memory. The kinetics and characteristics of the eosinophil response suggested that it was locally rather than systemically controlled. This conclusion is based on the fact that, in contrast to the situation seen after oral infection with T. spiralis, there was little change in bone marrow eosinophilopoiesis, blood eosinophil numbers or in serum interleukin-5 levels.

Animals↗
PubMed1977

Immune responses to influenza virus in rabbits after local immunization. i.--Local and systemic humoral response.

IgA was found to be the predominant immunoglobulin in the bronchoalveolar secretions of rabbits. Significant quantities of IgG antibodies were also present in these secretions after intratracheal immunization with live influenza virus, but IgA/IgG ratios in the secretions were always higher than in corresponding sera, whether the rabbits were immunized or not. The relative excretion coefficients of IgA in these secretions were also found to be higher. In vitro culture of broncho-alveolar wash cells showed active synthesis of all the three major immunoglobulins with IgG as the predominant one. Immunization with live influenza virus induced a higher and more persistant antibody response in the respiratory secretions than the inactivated virus. A rapid and more intense production of IgA and IgG antibodies in these secretions after intratracheal booster antigen strongly suggests the presence of immunological memory in the secretory immune system of the respiratory tract. The role of secretory antiviral antibodies in protection against respiratory infections is also discussed.

Animals↗
PubMed1995

[Particpation of apoptosis in immunologic processes].

Apoptosis is a biological process that leads certain cells to die in a controlled fashion. Its biochemical manifestation is DNA fragmentation due to the action of an endonuclease and morphological consequence is the formation of apoptotic bodies, seen with light or electron microscopy. Apoptosis is universally important in embryogenesis and morphogenesis of all tissues. Lately, a fundamental role of apoptosis in the physiology and physiopathology of immunological events has been uncovered. This review details the role of apoptosis in the development of auto-tolerance, immunological memory and AIDS pathogenesis.

Apoptosis↗
PubMed1977

Anti-larval antibodies in the serum and abomasal mucus of sheep hyperinfected with Haemonchus contortus.

A radioimmunoassay technique was used to follow the anti-larval antibody response in the serum of sheep subjected to repeated dosing with Haemonchus contortus. The response was found to develop slowly and seemed to decline as soon as the sheep stopped receiving larvae. No immunological memory was observed after the sheep were challenged with 4000 larvae nine weeks after daily dosing was stopped. Examination of abomasal mucus collected from the sheep at slaughter revealed the presence of IgA and IgG antibodies. It is suggested that most of this mucus IgG was derived from blood whereas the IgA was locally produced.

Abomasum↗
PubMedDate not supplied

Inhibition of established pancreatic cancers following specific active immunotherapy with interleukin-2 gene-transduced tumor cells.

Pancreatic cancer has a poor prognosis even when complete resection can be accomplished. Recent studies have demonstrated that the immune system is capable of mounting effective tumor-specific immune responses even against "nonimmunogenic" tumors. The studies reported herein were conducted to determine if induction of tumor-specific immune responses of inhibiting in vivo pancreatic tumor growth could be achieved through active immunization with pancreatic tumor cells genetically engineered to secrete interleukin-2 (IL-2). A relevant poorly immunogenic subcutaneous model of murine ductal pancreatic cancer was first developed using an implantable tumor cell line Panc02 in C57BL/6 mice. Panc02 cells were then genetically engineered to secrete human IL-2 (Panc02/IL2). The ability of irradiated Panc02/IL2 cells to stimulate an immune response capable of rejecting a subsequent tumor challenge was first demonstrated. Ninety percent of animals vaccinated with irradiated parental Panc02 and subsequently challenged with parental Panc02 cells developed tumors by 48 days (mean tumor volume of 234 mm3) compared to only 40% (P < .05, chi square) of animals vaccinated with irradiated Panc02/IL2 and challenged with parental Panc02 (14 mm3, P < .004, tau test). The therapeutic benefit of active immunization in tumor-bearing animals was then examined. Mice with 3-day-old established subcutaneous tumors were administered a series of 4 weekly vaccinations with irradiated Panc02 or Panc02/IL2 cells. A significant reduction in tumor growth was present in those animals vaccinated with Panc02/IL2 (P < .005, tau test) versus Panc02 or saline. Animals whose established tumors regressed following vaccinations with IL-2-secreting Panc02 cells were found to have long-lasting immunity as demonstrated by rejection of a tumor challenge presented over 140 days following inoculation of the primary tumor. We conclude that an immune response capable of inhibiting established pancreatic tumors can be generated by vaccination with IL-2-secreting tumor cells. Furthermore, long-term immunological memory was established in mice that rejected the original established tumor. These studies provide preclinical evidence to support the use of cytokine gene-transduced tumor cell vaccinations in patients with pancreatic cancer.

Adenocarcinoma↗
PubMedDate not supplied

Anti-estrogens potentiate the immunotherapy of the P815 murine mastocytoma by cytotoxic T lymphocytes.

Many animal and human tumors are infiltrated with killer cells. Recent studies have shown that the stimulation of such killer cells with interleukin-2 improves their tumor rejecting capacity. In this paper we demonstrate that the anti-estrogens, tamoxifen (TX) and toremifene (TO), enhance host resistance by sensitizing the tumor target to killer cell mediated lysis. The P815 mastocytoma syngeneic to DBA/21 mice was used. Cytotoxic T lymphocytes (CTL) were detected in the spleens of mice 12-14 days after tumor inoculation. In vitro target, effector, or both cell types were treated with either TX (1 microM) or TO (5 microM) for 4 hours prior to cytotoxicity testing by 51Cr release. Mice bearing P815 mastocytomas, 5 mm in diameter, were treated orally with TX or TO and were given CTL isolated from the spleens of tumor bearing donors i.p. Tumor growth, mortality, and immunological memory in cured animals were monitored. Both TX and TO treatment sensitized P815 target cells to lysis by CTL isolated from tumor bearing animals. The transfer of killer cells from the spleens of tumor bearing mice produced tumor suppression in the recipients, which could be enhanced by additional oral treatment by TX or TO. Complete cure was achieved in a significant number of animals, showing partial or complete resistance to a subsequent lethal dose of P815 cells. These experiments indicate that killer cells isolated from mice bearing progressive tumors can have an immunotherapeutic effect in syngeneic tumor bearing recipients and that the antiestrogens, TX and TO, may be used to potentiate the immunotherapy of this tumor.

Adoptive Transfer↗
PubMed1997

Immunization with bacterial antigens: infections with motile aeromonads.

Motile aeromonads are a heterogeneous group of organisms which are involved in a number of disease syndromes of warm water fish. They are commonly associated with bacterial haemorrhagic septicaemia, infectious dropsy, red mouth disease, ulcerative conditions etc. A variety of factors has been considered to be associated with virulence including haemolysins, proteases, surface array protein, acetylcholinesterase etc. We have studied the immune response of Indian major carps to antigens of motile aeromonads. The Indian major carp, Labeo rohita, showed immunological memory and secondary response on booster administration. The extent of protection showed good correlation with titres of agglutinating antibody. When polyvalent vaccine was used, the fish showed antibody titres against all the component strains. However, the level of antibody was less compared to immunization by monovalent vaccines. Cross-reacting antibodies induced by monovalent vaccines showed varying degrees of protection.

Aeromonas↗
PubMed1997

Full immunologic reconstitution following nonconditioned bone marrow transplantation for canine X-linked severe combined immunodeficiency.

Bone marrow transplantation in human X-linked severe combined immunodeficiency (XSCID) without pretransplant conditioning results in engraftment of donor T cells and reconstitution of T-cell function but engraftment of few, if any, donor B cells and poor reconstitution of humoral immune function. Since bone marrow transplantation remains the most effective treatment of XSCID patients, better strategies are necessary to achieve optimum long-term results. Canine XSCID, like human XSCID, is due to mutations in the common gamma chain (gamma c) gene and has clinical and immunologic features identical to those of human XSCID, making it a true homolog of the human disease. We have successfully performed bone marrow transplantation in three XSCID dogs without pretransplant conditioning, using untreated bone marrow cells from mixed lymphocyte culture-nonreactive normal littermates. Unlike the experience in human XSCID patients, all three dogs engrafted both donor B and T cells and attained full reconstitution of immunologic function. Normal percentages of T cells and T-cell mitogenic responses were attained by 3 months posttransplant. CD3+ T cells after transplantation expressed the CD45RA isoform indicating that the cells were recent thymic emigrants derived from immature progenitors. Serum IgG levels were within normal range by 5 months posttransplant. Immunization with the T-dependent antigen, bacteriophage phiX174, demonstrated normal antibody titers, immunologic memory, and class-switching. Polymerase chain reaction (PCR) analysis of the gamma c locus showed that 100% of circulating T cells and 30% to 50% of circulating B cells were donor-derived. None of the dogs developed clinically evident graft-versus-host disease (GVHD). Thus, canine XSCID provides a model to determine the optimal conditions for bone marrow transplantation in human patients, and to develop and test strategies for somatic gene therapy.

Animals↗
PubMed1976

Changes in spleen histology in response to antigenic stimulation in the snapping turtle, Chelydra serpentina.

Proliferative and migratory changes of lymphoid cells in the spleen were observed in turtles stimulated with KLH and maintained at 30 degrees C. Small foci of pyroninophilic lymphoblasts were first seen in the white pulp at about day 5. Progressive enlargement of these centers continued and peaked by days 8-12. By days 15-20 the white pulp returned to a normal (unimmunized) state, while the number of pyroninophilic cells, primarily plasma cells, increased markedly in the red pulp. At days 22-25, the number of plasma cells returned to normal levels and the spleen appeared normal for the remainder of the 60 day observation period. These events suggest that at 30 degrees C, the turtle is capable of a strong and prompt proliferative response in the white pulp sheaths, followed by migration and differentiation of lymphoblasts into plasma cells, in the red pulp. Observations of pyroninophilic cells in sinuses, venules and veins of the spleen and a concomitant depletion of cells in red pulp, further suggest a migration from the spleen to other sites. Following a second antigenic challenge, at day 60, no significant histological changes were observed at 30 degrees C. Nor were any changes observed following primary or secondary antigenic challenge, in animals maintained at 10 degrees C. These findings are discussed with regard to immunological memory and low temperature immunosuppression in ectothermic vertebrates.

Animals↗
PubMed1998

The relationship of blood lymphocytes to the recirculating lymphocyte pool.

Lymphocyte recirculation facilitates the detection and elimination of pathogens and the dissemination of immunologic memory. It is generally assumed that all small lymphocytes in the blood are actively recirculating, yet there is little quantitative data directly comparing the migration of this population with actively recirculating, lymph-derived lymphocytes. In this study blood lymphocytes were labeled with fluorescein isothiocyanate (FITC), and lymph lymphocytes were labeled with CM-DiI, reinfused intravenously, and monitored in blood and lymph. After equilibration the concentration of blood lymphocytes was several times higher in blood than in lymph, whereas lymph lymphocytes displayed the opposite behavior. This suggested that blood lymphocytes did not recirculate as efficiently as lymph lymphocytes, so we examined the following blood lymphocyte subsets in greater detail: B cells, CD4+, CD8+, and gammadelta T cells. Within 4 hours postinjection the percentage of FITC+ CD8+ and CD4+ lymphocytes fell in the blood and remained significantly lower than the injected sample. In contrast, the concentration of FITC+ gammadelta T cells did not change, and the percentage of FITC+ B cells increased. These data suggest that subpopulations of B and perhaps gammadelta T lymphocytes in the blood do not recirculate efficiently through lymph nodes.

Animals↗
PubMed1998

Allogeneic bone marrow transplantation: relation between chimaerism and immunity.

Bone marrow transplantation has been performed for almost 30 years in the Department of Paediatrics of the Leiden University Hospital. Major research efforts focussed on the accurate determination of the chimaerism and the immunological recovery of the graft recipient, and on the immunological interactions between donor and host cells. The results of our investigations and those of other groups in the field of bone marrow transplantation provided a lot of information on these topics, offering possibilities for improving the outcome of the patients by changing transplant procedures and developing novel preventive and therapeutic interventions. As was formerly shown in animal experiments, the conditioning of the graft recipient had to be tailored for the purposes of the bone marrow transplantation. It had to be either immunosuppressive, or space creating, or tumor eradicating, or a combination of these, in accordance with the original disease of the patient. It also became evident that the numbers of functional T lymphocytes remaining in the host and present in the graft had reciprocal effects on graft rejection (host-versus-graft) and graft-versus-host disease. Modification of the composition of the graft, e.g. by T-cell depletion, resulted in an increased rejection rate unless extra-immunosuppression was administered to the host. Vice versa, the occurrence and severity of graft-versus-host disease was very much dependent on HLA-matching between donor and recipient and on numbers of T cells in the graft. With regard to immune recovery after bone marrow transplantation, it was shown that the pretreatment of the host had to be adjusted to obtain engraftment of those cell lineages which were relevant for an adequate and complete immune competence of the host after bone marrow transplantation. This could nicely be illustrated by the relationship between B-cell engraftment and recovery of humoral immunity after HLA-haplo-identical bone marrow transplantation of young children, suffering from severe combined immunodeficiency disease. In later experiments our group showed that is was feasible to transfer specific immunological "memory" to vaccine antigens from donor to host by mature T cells in the graft and following priming of donor and host with the antigen prior to transplantation. Reversely, when T cells were taken out of the graft, reactivations of DNA-viruses such as CMV and EBV could be observed, frequently resulting in lethal infections. Also there was an increase of the frequency of leukaemia relapse after T-cell depleted bone marrow transplantation for leukaemia. In order to prevent these severe complications donor T-cell infusions have been tried with success, although also with an increase in occurrence and severity of graft-versus-host disease. Recent developments on the production ex vivo of virus-specific cytotoxic T cells and the transfer of these cells to the host, early after bone marrow transplantation, resulted in remarkable clinical effects. These observations open the way for further research, development and trials of adoptive immunotherapy for the prevention of leukaemia relapse after bone marrow transplantation of leukaemia patients. Also recently attention has been paid to the induction of microchimaerism with donor haemopoietic cells, following a relatively non-toxic one-day conditioning of the host, in order to attain a state of tolerance against a solid organ transplant. This possibly promising application of the presence of a blood cell chimaerism is at present under study in animal models.

Animals↗