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G Tufveson

Publications and source records attributed to G Tufveson.

198 records · Page 11Linked to original sources

T-lymphocyte subsets and HLA-DR-expressing cells in rejected human kidney grafts.

This communication describes an immunohistochemical analysis of rejected human renal allografts. T-lymphocyte subsets were identified in frozen tissue sections, by Leu 1 (anti-'pan' T lymphocytes), Leu 2a (anti-'cytotoxic/suppressor' T cells), and Leu 3a (anti-'helper/inducer' T cells) monoclonal antibodies. In addition, HLA-DR-positive cells were identified by simultaneous labelling with heterologous anti-HLA-DR antibodies. T cells dominated the cellular infiltrates in acute cellular rejection. Leu-3a-positive cells were more numerous than Leu-2a-positive cells. The Leu-3a-positive cells usually appeared in clusters, whereas the Leu-2a-positive cells appeared scattered in the tissue. HLA-DR-positive non-T cells were found within clusters of T 'helper/inducer' cells. The cell pattern shares many features with the findings in delayed-type hypersensitivity reactions.

Antibodies, Monoclonal↗

Lymphoma development from transplanted murine leukemia virus infected organ cultured thymuses: inhibitory effect of in vitro interferon treatment.

Thymuses of 14-day-old AKR mouse embryos were infected with Gross murine leukemia virus (MuLV) and then maintained in organ culture for 3 weeks. When they were transplanted to 3-week-old (AKR X C3H)F1 mice, approximately 50% of these developed T lymphomas within 3-4 months. Most (22/23) tumors were of host, F1-hybrid, origin while only one was of donor AKR type. No clear evidence for in vitro MuLV-induced lymphoma cells was therefore obtained. Exposure of MuLV-infected embryonic thymuses to interferon during the organ culture period significantly reduced the incidence of lymphomas in mice receiving such thymus transpalnts. Interferon also prevented the appearance of detectable numbers of MuLV antigen-containing lymphocytes in infected organ-cultured thymuses. In contrast, despite the use of very high interferon concentrations, no effects were seen on the number of viable thymic lymphocytes, their proliferation or responsiveness to the polyclonal T-cell mitogens concanavalin A (Con A) and leukoagglutinin (LA). Thus interferon, presumably through an antiviral effect, can limit the MuLV infection in the thymus and its consequence, i.e. development of a lymphoma.

AKR murine leukemia virus↗

Role of the thymus in generation of lymphocyte functions. III. Further studies of the alloreactivity of lymphocytes developing in mouse thymus organ cultures.

Thymuses of 14-day-old mouse embryos could be maintained in organ culture, using serum-free medium, with generation of lymphocytes that showed strong proliferative reactivity to allogeneic spleen cells in mixed lymphocyte cultures (MLC). Such organ culture derived thymocytes also developed cytotoxic activity against target cells carrying the alloantigens of the stimulating spleen cells in the MLC. The generated cytotoxic activity was, however, proportionately lower than that seen with thymocytes of young mice. A time course study showed that cells with apparent reactivity to both allogeneic spleen cells and to the mitogen Concanavalin A (Con A) first appeared in the thymus organ cultures on day 8-9.

Animals↗

Natural cell-mediated immunity to lymphoma cells. I. Characteristics of effector cells in a cytostasis assay in vitro.

Spleen cells from normal, nonimmune, CBA or (CBA X AKR)F1 mice markedly and rapidly inhibited the incorporation of [3H]thymidine by two different T-cell lymphomas in an in vitro cytostasis assay. These were the I-529 lymphoma of spontaneous AKR origin and the Moloney murine leukemia virus-induced YAC lymphoma of A mouse origin. Spleen cells were the most efficient inhibitors for both types of target cells, whereas lymph node cells were much less active and thymus cells showed little or no activity. Granulocytes, as well as conventional T- and B-lymphocytes, were excluded as important contributors to the cytostatic cell population. Spleen cells were separated on nylon wool, Sephadex G-10 columns, or plastic petri dishes and tested for activity in the cytostasis assay or for cytotoxicity against 51Cr-labeled lymphoma target cells. Adherent cells carried almost all cytostatic activity against the AKR lymphoma but also showed significant cytotoxic activity against these target cells. In addition, the cytostatic activity against the YAC lymphoma was mainly due to adherent spleen cells, but nonadherent cells were relatively more active against this target than against I-529 cells. Such nonadherent spleen cells further showed increased cytotoxic activity, compared to the whole spleen cell population.

Animals↗

In vitro establishment and some properties of AKR thymoma cell lines.

Lymphoid cell lines could easily be directly established in vitro from spontaneous thymomas of aged AKR mice. The established lines all carried the Thy-1.1 antigenic marker of T lymphocytes. They differed markedly, however, from one another in several respects. Thus, they showed high or low quantity of Thy-1.1 antigens per cell, high or low sensitivity to cortisone and thymidine, as well as differing morphology and growth rate. The observed heterogeneity suggests that such AKR thymoma cell lines may provide a valuable tool to study T lymphocyte properties and the biology of the AKR thymoma, in particular non-immune and immune mechanisms influencing thymoma cell growth.

Animals↗

Role of the thymus in generation of lymphocyte functions. I. Demonstration of lymphocytes reactive to mitogens and allogeneic cells in the embryonic mouse thymus in organ culture.

The thymuses of 14-day-old CBA mouse embryos cultured for 14 days in organ cultures supplemented with mouse serum contained lymphocytes that were highly reactive to the mitogens concanavalin A (Con A) and leukoagglutinin (LA) and to irradiated allogeneic spleen cells in vitro. In contrast, thymocytes derived from fetal-calf-serum-supplemented organ cultures displayed much weaker responses to the two mitogens and little or no response to the allogeneic spleen cells. Control thymocytes obtained from 1-month-old CBA mice responded well to Con A but not to LA. The responses of these cells to allogeneic spleen cells were delayed compared with the organ-culture-derived cells, which responded promptly, with a maximum already on culture day 2-3. The results demonstrate that the organ culture system provides a convenient model for further study of the generation of immunoreactive cells in the mouse thymus.

Animals↗

Ontogeny of spontaneous rosette-forming cells in the chicken. With special reference to the bursa of Fabricius.

Cells forming rosettes (RFC) with sheep erythrocytes (SRBC) and rabbit erythrocytes (RRBC) were studied during the ontogeny of the bursa of Fabricius of the chicken. The frequency of SRBC-RFC was low but significant in the bursa of 15-day-old embryos, and increased therafter in an approximately linear fashion with the age of the bursa donor until at least in 43-day-old chickens. The total number of SRBC-RFC per bursa increased throughout the ontogeny with no evidence for any abrupt increase after hatch. The mean number of SRBC bound per RFC also increased after hatch. In contrast the frequency of bursal RRBC-RFC was high in 15-day-old embryos, significantly decreased on embryonic day 18, remained low until at least 7 days after hatch and then increased significantly. The total number of RRBC-RFC per bursa in contrast remained relatively constant during the embryonic period and the first week after hatch and thereafter increased markedly. No change in the mean number of RRBC bound per RFC could be demonstrated during the ontogeny. RRBC-RFC were also frequent in the yolk sac, spleen, and thymus of 15-day-old embryos.

Age Factors↗

Spontaneous rosette-forming cells in the chicken. Tissue distribution, binding characteristics and bursa dependency.

The frequency and binding characteristics of cells spontaneously forming rosettes (RFC) with rabbit erythrocytes (RRBC) and sheep erythrocytes (SRBC) in different tissues of 6-week-old chickens were studied. RFC were most frequent in the bursa of Fabricius, followed in order by the spleenpquent than SRBC-RFC. The number of erythrocytes (RBC) bound by each RFC was also determined. The mean binding capacity of the RFC for either RRBC or SRBC did not differ between the different tissues. The distribution of the RFC into classes binding different numbers of RRBC was similar for all analysed tissues. Howeverthe corresponding distribution for the SRBC-RFC was considerably more heterogeneous. Embryonic surgical (S-Bx) or cyclophosphamide (Cy-Bx) induced bursectomy much reduced the frequencies of RFC binding SRBC in the spleen. The frequency of RRBC-RFC was not altered by these procedures. S-Bx reduced the frequency of spleen RFC binding lightly but not heavily trinitrophenyl-haptenized (TNP) SRBC, whereas Cy-Bx reduced the frequency of the latter RFC type.

Absorption↗

Effects of mitogens for mouse B lymphocytes on chicken lymphoid cells.

Lipopolysaccharide from E. coli (LPS) and purified protein derivative from tuberculin (PPD) increased the [3H]thymidine incorporation of chicken spleen cells in culture. No such stimulation was observed with dextran sulphate. Thymus and bursa lymphocytes were not stimulated by any of these compounds. Spleen cells from chickens chemically bursectomized with cyclophosphamide treatment showed decreased responses to LPS and PPD, but responded normally to the T-cell mitogen concanavalin A. None of the tested mitogens induced polyclonal antibody synthesis or directly enhanced the primary antibody response to sheep erythrocytes (SRBC) in spleen cell cultures. LPS-coated SRBC, however, enhanced the in vitro antibody response to SRBC. The results suggest a moderate proliferative response of chicken lymphocytes to LPS and PPD, possibly involving B cells, but not further effects comparable to those on mouse B lymphocytes.

Animals↗

Delayed graft function: risk factors, consequences and parameters affecting outcome-results from MOST, A Multinational Observational Study.

BACKGROUND: Delayed graft function (DGF) is a common complication after renal transplantation, and may affect graft function. The aim of this analysis was to evaluate risk factors for DGF, as well as parameters and events influencing graft function after DGF. We analyzed data collected in an ongoing international, prospective; observational study, the Neoral-MOST (Multinational Observational Study in renal Transplantation), and included in the analysis all patients with cadaveric kidney transplants for whom renal function at 1 year posttransplantation was documented (N = 8950). Logistic regression was used to evaluate the risk factors for DGF occurrence, and multifactorial analysis of variance (ANCOVA) to assess the relevance of different factors for GFR at 1 year. RESULTS: Higher donor age, longer CIT, male recipients, Caucasian recipients, high recipients body mass index, and PRA were all associated with a higher risk for DGF. Renal function of former DGF kidneys at 1 year was lower in kidneys of elder donors, or which had experienced rejection or CMV infection. Variations of the maintenance regimen at 1 year posttransplantation were not associated with better graft function. Multifactorial analysis showed donor age and acute rejection as significant independent factors. CONCLUSIONS: Most factors increasing the risk for DGF or having a negative impact on renal function at 1 year in grafts with DGF are predetermined. Additional posttransplant damage by acute rejection was associated with further reductions in GFR. Preventing acute rejection is an important step in achieving optimal function of DGF grafts.

Adult↗

Impact of mycophenolate mofetil dose posttransplantation on 12-month renal function: analysis of the MOST database.

INTRODUCTION: Mycophenolate mofetil (MMF) has greatly reduced the risk of acute rejection episodes (ARE) after renal transplantation, but dose reductions/withdrawals could jeopardize long-term results. METHODS: The MOST database of "de novo" patients treated with MMF at month 1 and functioning grafts at month 12 were divided into 2 groups: groups 1, 2 g MMF at month 1 and month 12; and group 2, 2 g MMF at month 1 but MMF <2 g at month 12 to evaluate renal function glonerular filtration rate (GFR). RESULTS: In this study, 1136 patients were receiving 2 g MMF at month 1. On month 12, 645 were on 2 g (56.8%, group 1) and 431 were on <2 g (43.2%, group 2). Group 1 included younger recipients of younger donors with fewer patients with delayed graft function (DGF). Group 1 showed more ARE during month 1 and more patients who received induction. Mean Neoral daily doses at month 1/month 12 were 5.3/3.0 and 5.3/3.1 mg/kg in group 1 and group 2, respectively (P = .05 at month 12). GFR in group 1 and group 2 were 59.06 (CI 57.10-60.60) and 53.81 (CI 52-55.7) at month 1 (P < .001); 63.7 (CI 62.1-65.30) and 55.9 (CI 54.1-57.7) mL/min*1.73 m(2) at month 12 (P < .001). The mean increases in GFR between month 1 and month 12 were 4.64 and 1.94 mL/min*1.73 m(2), respectively (P < .05). A multivariate analysis also included 795 patients from the "maintenance" patient database with retrospective detailed information. The following parameters were highly predictive for good renal function at month 12: donor age younger than 60 years, recipient age younger than 60 years, immediate graft function, 12-month MMF dose = 2 g, absence of CMV infection, and 12-month Neoral dose <3 mg/kg/d. CONCLUSIONS: Maintenance of MMF dose at 2 g/d during the first year appears to facilitate the attainment of optimal renal function at 12-months after kidney transplantation.

Analysis of Variance↗

Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation.

BACKGROUND: Intraportal transplantation of pancreatic islets offers improved glycaemic control and insulin independence in type 1 diabetes mellitus, but intraportal thrombosis remains a possible complication. The thrombotic reaction may explain why graft loss occurs and islets from more than one donor are needed, since contact between human islets and ABO-compatible blood in vitro triggers a thrombotic reaction that damages the islets. We investigated the possible mechanism and treatment of such thrombotic reactions. METHODS: Coagulation activation and islet damage were monitored in four patients undergoing clinical islet transplantation according to a modified Edmonton protocol. Expression of tissue factor (TF) in the islet preparations was investigated by immunohistochemistry, immunoprecipitation, electron microscopy, and RT-PCR. To assess TF activity in purified islets, human islets were mixed with non-anticoagulated ABO-compatible blood in tubing loops coated with heparin. FINDINGS: Coagulation activation and subsequent release of insulin were found consistently after clinical islet transplantation, even in the absence of signs of intraportal thrombosis. The endocrine, but not the exocrine, cells of the pancreas were found to synthesise and secrete active TF. The clotting reaction triggered by pancreatic islets in vitro could be abrogated by blocking the active site of TF with specific antibodies or site-inactivated factor VIIa, a candidate drug for inhibition of TF activity in vivo. INTERPRETATION: Blockade of TF represents a new therapeutic approach that might increase the success of islet transplantation in patients with type 1 diabetes, in terms of both the risk of intraportal thrombosis and the need for islets from more than one donor.

Adult↗

Expression of an interferon-gamma-like substance in normal and transplanted rat heart tissue.

The presence of interferon-gamma-like molecules has been reported not only in lymphocytes, but also in certain nerve cells and in normal skeletal muscle. We have studied the reactivity of the anti-interferon-gamma monoclonal antibody DB1 with frozen sections of normal and transplanted rat hearts. Cardiac grafts from PVG donor rats were transplanted to syngeneic PVG recipients or allogeneic Wistar/Kyoto recipient rats with the use of an accessory cervical heart transplantation technique. The allogeneic heart transplants were harvested 4 days and the syngeneic grafts 4 weeks after transplantation. In normal hearts there was a weak but distinct reactivity with the anti-interferon-gamma antibody in most muscle cells. In addition, some lymphocytes and the Purkinje fibers were positive. Hearts transplanted over an allogeneic barrier revealed that staining for interferon-gamma on muscle cells was substantially increased whereas no or only a moderate increase in the anti-interferon-gamma staining was seen in hearts transplanted to syngeneic recipients. These data indicate that interferon-gamma present in rat myocyte may be involved in the pathophysiology of graft rejection and also suggest that interferon-gamma may be of importance for the function of normal rat heart muscle cells.

Animals↗