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Biomedical subjects

R A Good

Publications and source records attributed to R A Good.

At least 289 records · Page 16Linked to original sources
PubMed1987

An epitope on class II antigens that is maintained across species barriers and important in immunologic functions.

Serological, functional, and chemical analyses of murine class II antigens were performed using a unique monoclonal antibody, 1E4, which was obtained from a rat-mouse hybridoma. 1E4, which is specific for a monomorphic determinant on HLA-DR antigens in humans and a polymorphic determinant on RT1-Da antigens in rats, detected class II antigens on the cells from mice carrying H-2 haplotypes of b, d, p, q, u, v, k, j, r, but not those with f or s haplotypes. Analysis of two-dimensional gel electrophoresis revealed that 1E4 monoclonal antibody recognized at least Ek/b, d, k and Ab, d molecules. 1E4 blocked the T cell proliferative responses to beef insulin and TGAL in B10 and BALB/c mice, as well as proliferative responses to GLT in BALB/c mice and to PPD in C3H/He mice, as had been demonstrated in other species. Furthermore 1E4 inhibited MLR to stimulator cells that expressed Ab, d or Ek/b, k, d molecules. Taken together, these findings indicate that an epitope detected by 1E4 on class II antigens has been well preserved across species barriers. This epitope may play a major role or be closely related to the functional site that is involved in recognition of nominal antigens by T cells.

Animals↗
PubMed1987

Risk factors for acute graft-versus-host disease.

Acute graft-versus-host disease (GvHD) is an important complication of bone marrow transplantation in humans. Risk factors are imprecisely defined and controversial. We analysed data from 2036 recipients of HLA-identical sibling transplants for leukaemia or aplastic anaemia to identify risk factors for GvHD. Analyses indicate that grading of GvHD can be reproducibly divided into absent or mild versus moderate to severe; 2-year actuarial probability was 54% (95% confidence interval 52-56%) for absent or mild and 46% (44-48%) for moderate to severe. Factors predictive of development of moderate to severe GvHD include donor/recipient sex-match (female----male greater than others, relative risk 2.0, P less than 0.001). This risk was markedly increased if female donors for male recipients were previously pregnant or transfused (relative risk 2.9, P less than 0.0001). Older patients were at increased risk of GvHD (relative risk 1.6, P less than 0.001), but the age gradient was modest, even the youngest patients had a substantial risk of GvHD and, if parous or transfused female----male transplants were excluded, age was not a significant risk factor. Cyclosporine or methotrexate were equally effective at preventing GvHD and were superior to no prophylaxis (relative risk 2.3, P less than 0.01). These data should be useful in estimating the risk of acute GvHD in an individual patient and in designing clinical trials to investigate methods to modify or prevent GvHD.

Acute Disease↗
PubMed1987

Influence of inactivated feline retrovirus on feline alpha interferon and immunoglobulin production.

The effect of ultraviolet-inactivated feline leukaemia virus (UV-FeLV) on the development of feline immunoglobulin-secreting cells (ISC) was investigated using a reverse haemolytic plaque assay. Low concentrations of UV-FeLV at 2 X 10(-4) to 2.0 micrograms/ml stimulated the production of ISC. By contrast, the same concentration of UV-FeLV suppressed the development of pokeweed mitogen (PWM)-driven ISC. Maximum suppression of ISC occurred at 50 micrograms/ml of UV-FeLV. The generation of an interferon resistant to acid, heat and sodium dodecyl sulphate (SDS) in the media of lymphocyte cultures incubated with PWM was also significantly suppressed in the presence of 0.2 microgram/ml of UV-FeLV. These findings suggest that non-infectious viral particles appear to modify feline immunoglobulin and interferon-secreting systems.

Animals↗
PubMed1987

Clearance of retroviremia and regression of malignancy in cats with leukemia-lymphoma during treatment with staphylococcal protein A.

Cats persistently infected with a type C retrovirus (feline leukemia virus; FeLV) were treated either by the extracorporeal perfusion of their plasma through filter columns containing staphylococcal protein A (SPA) or by the intraperitoneal injection of SPA for up to 32 treatments. The clearance of evidence of viral infection occurred during treatment with SPA in 67% of the treated cats with chronic viral infection that had FeLV-related abnormalities other than overt malignancy. This rate of viral clearance is more than 30 times greater than the incidence of spontaneous clearance of persistent FeLV viremia in the untreated cat. Actual clearance of viremia occurred in 28% of all cats treated. Regression of malignancy, which occurred in four of 12 (33%) treated cats, was demonstrated by reductions in tumor size and bone marrow neoplastic cell populations. Immediately preceding or concurrent with these remissions from viral infection and malignant disease, a marked though transient elevation in the plasma level of circulating gamma-like interferon occurred in some responding cats and was followed by the appearance and rising titer of a complement-dependent cytotoxic antibody that reacted with FeLV-infected cells. This IgG antibody was shown by several analyses to be specific for the major viral envelope glycoprotein gp70. Further investigations demonstrated that high levels of FeLV at the cellular level might be responsible for the reduced ability of normal feline lymphocytes to secrete gamma-interferon in response to mitogenic stimuli in vitro. These findings may provide some clue to the variation in the responsiveness of individual cats to immunotherapy with staphylococcal protein A.

Animals↗
PubMed1987

Treatment of systemic and organ-specific autoimmune disease in mice by allogeneic bone marrow transplantation.

Autoimmune diseases have been clinically divided into those which are systemic and organ-specific. (NZB X NZW) F1, MRL/1, and BXSB mice have been utilized as models for systemic autoimmune diseases. When these mice which had already developed autoimmune diseases were irradiated and reconstituted with T cell-depleted allogeneic bone marrow cells, the recipient survived for more than 5 months without showing graft-versus-host reaction. Immunohistopathological studies revealed that deposits of immunoglobulin and complement into the glomeruli were markedly reduced. In addition, levels of circulating immune complexes and auto-antibodies such as anti-dsDNA and anti-Sm antibodies decreased. Three months after bone marrow transplantation, T cell dysfunction was restored, and hyperfunction of B cells and macrophages were normalized. These data prompted us to examine whether or not organ-specific autoimmune diseases can be treated by allogeneic bone marrow transplantation. NOD mice which develop insulitis and overt diabetes were used for this experiment. The mice showed marked infiltration of T cells into the pancreatic islets which resulted in selectively destroying beta cells. Most of the T cells are Lyt-1+, and some are Lyt-2,3+. When NOD mice (6 months old) were irradiated and reconstituted with bone marrow cells of young BALB/c nu/nu mice (less than 2 months), the NOD mice exhibited neither insulitis nor overt diabetes. Deposits of immunoglobulin in the mesangial area of the glomeruli disappeared 3 months after bone marrow transplantation. Assays for immunological functions revealed that NOD mice showed hyperfunction of T cells, B cells, and macrophages. In NOD mice reconstituted with BALB/c nu/nu bone marrow cells, these functions were normalized. Newly developed T cells are found to be tolerant of both bone marrow donor-type and host-type major histocompatibility complex determinants. These results suggest that bone marrow transplantation is a strategy to be considered as an approach to the treatment for both systemic and organ-specific autoimmune diseases in humans.

Animals↗
PubMed1987

Successful pancreatic allografts in combination with bone marrow transplantation in mice.

We have established a new method for pancreatic allografts in mice by combining pancreatic transplantation with allogeneic bone marrow transplantation. In this approach, we first transplanted bone marrow to induce tolerance to both donor-type and host-type major histocompatibility complex (MHC) determinants. Pancreatic tissue from the same mouse strain as bone marrow donor was then grafted under the renal capsule. Acceptance of the grafts was confirmed by histopathological and immunohistochemical techniques. BALB/c mice reconstituted with C57BL/6J bone marrow cells accepted pancreatic tissue from both bone marrow donor (C57BL/6J)-type and host (BALB/c)-type mice. An immunohistochemical study revealed the presence of functional islets under the renal capsules. Assays for both mixed lymphocyte reaction (MLR) and induction of cytotoxic T lymphocytes indicated that the newly developed T cells are tolerant of both donor (stem cell)-type and host-type MHC determinants. By contrast, the T cells of these chimeras showed a significant responsiveness to third party MHC determinants. These findings suggest that pancreatic allografts combined with bone marrow transplantation may become a viable strategy for the treatment of patients with diabetes or patients who have undergone pancreatectomy.

Animals↗
PubMed1986

Anti-bacterial immunity to Listeria monocytogenes in allogeneic bone marrow chimera in mice.

Protection and delayed-type hypersensitivity (DTH) to the facultative intracellular bacterium Listeria monocytogenes (L.m.) were studied in allogeneic and syngeneic bone marrow chimeras. Lethally irradiated AKR (H-2k) mice were successfully reconstituted with marrow cells from C57BL/10 (B10) (H-2b), B10 H-2-recombinant strains or syngeneic mice. Irradiated AKR mice reconstituted with marrow cells from H-2-compatible B10.BR mice, [BR----AKR], as well as syngeneic marrow cells, [AKR----AKR], showed a normal level of responsiveness to the challenge stimulation with the listeria antigens when DTH was evaluated by footpad reactions. These mice also showed vigorous activities in acquired resistance to the L.m. By contrast, chimeric mice that had total or partial histoincompatibility at the H-2 determinants between donor and recipient, [B10----AKR], [B10.AQR----AKR], [B10.A(4R)----AKR], or [B10.A(5R)----AKR], were almost completely unresponsive in DTH and antibacterial immunity. However, when [B10----AKR] H-2-incompatible chimeras had been immunized with killed L.m. before challenge with live L.m., these mice manifested considerable DTH and resistance to L.m. These observations suggest that compatibility at the entire MHC between donor and recipient is required for bone marrow chimeras to be able to manifest DTH and protection against L.m. after a short-term immunization schedule. However, this requirement is overcome by a preceding or more prolonged period of immunization with L.m. antigens. These antigens, together with marrow-derived antigen-presenting cells, can then stimulate and expand cell populations that are restricted to the MHC (H-2) products of the donor type.

Animals↗
PubMed1986

Characterization of a newly established feline lymphoma-derived cell line (BKD) lacking T and B cell surface markers.

A new feline lymphoma-derived cell line, designated BKD, was isolated from an anterior mediastinal tumor. Cells of this line were characterized as lymphoid based on morphology, the lack of intracellular esterase and peroxidase activity, and absence of phagocytic function. In contrast with other established feline lymphoma-derived cell lines, cells of the BKD line lack characteristics of both feline T-cells and B-cells in that they neither form rosettes with guinea pig erythrocytes nor have demonstrable surface or cytoplasmic immunoglobulin. Approximately one third of BKD cells form EAC rosettes, a significant number of rosette forming cells (p = 0.0001) when compared to background sheep E-rosetting activity. In addition, a consistently titratable level of interleukin-2-like activity was produced when BKD cells were coincubated with concanavalin A and phorbol-12-myristate-13-acetate. Chromosome analysis showed that a majority of BKD cells are diploid. This new cell line has been continuously replicating in culture for over one year and produces feline leukemia virus as demonstrated by several analyses.

Animals↗
PubMed1986

Studies of immune responses in mice prone to autoimmune disorders. II. Decreased down-regulation by auto-anti-idiotype antibody in autoimmune-prone mice.

Three lines of evidence are presented which suggest that autoimmune-prone mice are deficient in the production of auto-anti-idiotype antibody during their immune response to trinitrophenylated Ficoll (TNP-F). NZB, MRL lpr/lpr and older BXSB male mice have no hapten-augmentable plaque-forming cells (PFC). Hapten-augmentable PFC have been previously shown to be cells whose secretion of antibody has been inhibited by the binding of auto-anti-idiotype antibody to cell surface idiotype. Sera from TNP-F immunized NZB mice lack PFC inhibiting activity (anti-idiotype antibody). Spleen cells from TNP-F immune NZB mice fail to transfer anti-idiotype antibody-mediated suppression to naive mice as do spleen cells from immune non-autoimmune-prone mice. Taken together these data suggest that autoimmune-prone mice are deficient in auto-anti-idiotype antibody-mediated downward regulation of their immune responses. It was further shown that the immune response of NZB mice to TNP-F shows a slower decline in splenic PFC and a greater heterogeneity of PFC affinity than do the responses of non-autoimmune-prone strains. Since athymic (nude) mice, which were previously shown to be defective in the production of auto-anti-idiotype antibody, also show a slower decline in splenic PFC and an increased heterogeneity of PFC affinity, it is suggested that these peculiarities of the immune responses of autoimmune-prone and athymic mice are also the consequences of the lack of auto-anti-idiotype antibody-mediated down-regulation.

Animals↗
PubMed1986

Leukemia prevention and long-term survival of AKR mice transplanted with MHC-matched or MHC-mismatched bone marrow.

The current studies were designed to evaluate the effectiveness of marrow transplantation within and outside the major histocompatibility complex (MHC) on the long-term survival and occurrence of spontaneous leukemia in AKR mice. AKR mice, which were lethally irradiated and received MHC-matched marrow from CBA/J mice (CBA----AKR), never developed leukemia and were alive and remained healthy for up to 280 days post-transplant. These long-term surviving chimeras possessed substantial immune vigor when both cell-mediated and humoral responses were tested. Lethally irradiated AKR mice, which had received MHC-mismatched marrow (anti-Thy-1.2 treated or nontreated) from C57BL/6J mice (B6----AKR), never developed leukemia and survived up to 170 days post-transplant. However, both groups of these chimeras began dying 180 to 270 days post-transplant due to a disease process which could not be readily identified. Histological analysis of B6----AKR chimeras revealed severe lymphoid cell depletion in thymus and spleen; however, none of these chimeras exhibited classical features of acute graft versus host disease. Concanavalin A mitogenesis, primary antibody responses to sheep red blood cells and the production of interleukin 2 (IL-2) were suppressed in B6----AKR chimeras. IL-2 treatment of B6----AKR chimeras was shown to partially correct these deficiencies without stimulating mixed lymphocyte responsiveness to donor or host lymphocytes. These studies indicate that the use of MHC-mismatched marrow for the prevention of spontaneous AKR leukemia may rely on augmentative IL-2 therapy for complete immune reconstitution of leukemia-free chimeras.

AKR murine leukemia virus↗
PubMed1986

Natural killer cells in the blood and bone marrow of the rhesus monkey.

Natural killer (NK) cells in peripheral blood lymphocytes (PBL) and bone marrow (BM) cells of the rhesus monkey were detected by their functional activity against K562 cells. Animals could be grouped into "high" or "low" NK responders, a trait found to be consistent over a period of 2 years. NK active cells in PBL were in the nonadherent population, with the majority bearing Fc receptors and a further subdivision of these into CR+ (complement receptor) and CR- NK cells. Of 10 monoclonal antibodies directed against different epitopes of human lymphocytes, OKT11, OKT10, and Leu 11 showed reactivity with rhesus NK cells. Only OKT10 was reactive with the effector site of the cell, as shown by its capability to block NK function. Of the Leu 11 monoclonal antibodies (a, b, c), Leu 11c was nonreactive while Leu 11a and Leu 11b were shown by immunofluorescence to bind to 7 to 21% of PBL; Leu 11b was also cytotoxic to the NK cells. Leu 11b did not prevent binding of Leu 11a to PBL, suggesting reactivity of these antibodies with different epitopes. Percoll fractionation of PBL and BM revealed a greater enrichment of NK activity with BM; also, with PBL peak NK activity occurred in fractions 4 and 5 while this occurred in fraction 5 with BM. Although Percoll PBL fractions contained a higher percentage of Leu 11b cells, the NK activity of the BM fractions was proportionately greater. The majority of PBL cells with NK activity were FcR+ while significant activity could be attributed to FcR- cells of BM, in both the unseparated and Percoll fractions of each tissue. The data suggest NK active cells of BM may be distinct from those found in PBL.

Animals↗
PubMed1986

Immunomodulation of human leukocytes by staphylococcal enterotoxin A: augmentation of natural killer cells and induction of suppressor cells.

Staphylococcal enterotoxin A (SEA), a protein isolated from culture supernatants of Staphylococcus aureus, is a potent T-cell mitogen and an inducer of interferon-gamma (IFN-gamma). We report here that SEA exhibits a number of significant in vitro immunomodulatory functions. In vitro treatment of human peripheral blood monocyte-depleted lymphocytes with SEA resulted in significant augmentation of their natural killer cytotoxicity against target cells from hemopoietic (K562, Daudi) or solid (melanoma, lung, colon) human tumor cell lines. SEA was found to be more effective than interferons-alpha (natural or Escherichia coli-derived) in augmenting natural killer (NK) cytotoxicity of peripheral blood lymphocytes. Studies on the kinetics of the augmentation revealed a significant increase of NK within 3 hr of in vitro treatment with SEA at 37 degrees C. A neutralizing monoclonal antibody specific for human IFN-gamma did not affect the augmentation of natural killer cytotoxicity by SEA, suggesting that SEA augmented natural killer cytotoxicity primarily by a mechanism not involving induction of interferon-gamma. Furthermore, in vitro treatment with SEA resulted in significant augmentation of antibody-dependent cell-mediated cytotoxicity and of natural killer-like cytotoxicity, generated in mixed lymphocyte culture, against the K562 targets. Induction of suppressor cells to proliferative responses of autologous or allogeneic mononuclear cells to phytohemagglutinin (PHA) or to allogeneic cells in mixed lymphocyte culture was observed after in vitro treatment of peripheral blood mononuclear leukocytes with SEA for 24 or 48 hr at 37 degrees C. In addition, the presence of SEA in mixed lymphocyte cultures (MLC) resulted in significant inhibition of the generation of specific T-cell-mediated cytotoxicity in MLC. These results suggest that SEA, which may be involved in S. aureus infections and in treatment with extracorporeal perfusion systems over S. aureus columns, can regulate a number of significant lymphoid functions.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1986

Changing manifestations of a chronic feline haematopoietic proliferative disease during immunotherapy with staphylococcal protein A.

A cat with feline leukaemia virus-associated malignant disease was treated by ex vivo immunoadsorption using staphylococcal protein A coated filters. During the 12-week course of treatment, the morphological manifestations of the haematopoietic disease showed a progressive transition from erythroid to myeloerythroid to myeloid predominance, and the disease was preceded by and associated initially and terminally with a blast transformation of lymphoblastic morphology. Necropsy revealed massive meningo-cerebral, as well as hepatic, renal, myeloid, lymphoid, peritoneal and pelvic infiltrations largely consisting of lymphoblastic cells. Evidence of myeloid and erythroid differentiation was present in all the infiltrates. The several possible bases for this shift of morphological expression are considered.

Animals↗
PubMed1986

Effect of intravenous immune globulin on natural killer cell activity: possible association with autoimmune neutropenia and idiopathic thrombocytopenia.

Natural killer cell (NK) activity was assessed in patients before and after treatment with intravenously administered immune globulin (IVIG). In eight patients with hypogammaglobulinemia or agammaglobulinemia receiving 300 mg/kg/dose IVIG every 4 weeks, NK activity was significantly lower after therapy than before. In two patients, one with idiopathic thrombocytopenic purpura and one with autoimmune neutropenia, receiving high doses (2 gm/kg) of IVIG, NK activity was unusually high before therapy. After treatment, NK activity decreased in correlation with the clinical response and elevation of peripheral cell counts. These data show that IVIG diminishes NK activity in vivo and that reduction of NK activity may be associated with clinical improvement in idiopathic thrombocytopenic purpura and autoimmune neutropenia. NK activity of lymphocytes obtained from healthy volunteers was reduced by the same concentrations of maltose or sucrose present in Gamimune or Sandoglobulin, respectively; IVIG preparations, however, were more inhibitory. The diminution of NK activity therefore may be related to two components of IVIG preparations, monomeric IgG and maltose or sucrose.

Adolescent↗
PubMed1986

Reconstitution of in vitro humoral immune function in bone marrow transplant recipients.

The process by which humoral immune function is re-established following bone marrow transplantation was investigated in 50 transplant recipients. The recovery of in vitro-specific antibody production directed at sheep red blood cells was found to proceed through three phases. B cell function and helper T cell function were undetectable in the first phase (encompassing the first 5 months after transplantation), in which only suppressor cells reached functional maturity. Suppressor cells controlled responsiveness in the second phase (encompassing the period 5 to 15 months postgrafting). During this period, B cells and helper T cells became fully responsive; their activity became measurable, however, only after removal of Sephadex G-10-adherent suppressor cells. Normal responsiveness (associated with the loss of excessive suppressor cell activity) was characteristic of the third phase (over 15 months posttransplantation). Particular attention was paid to the role of suppressor cells in the recovery of humoral immune function. Their activity was positively correlated with graft-versus-host disease (GVHD), particularly of the chronic type. Suppressor cell activity in the early posttransplant period was predominantly mediated by OKT8-positive T lymphocytes, whereas suppressor cell activity in chronic GVHD patients was predominantly mediated by peripheral blood mononuclear cells that were retained on Sephadex G-10 columns, but did not express OKT8 antigen.

Acute Disease↗
PubMed1986

Generation of cytotoxic T lymphocyte responses to allo-H-2 antigens in allogeneic bone marrow chimeras histocompatible at the H-2 subregions.

The present study was performed to determine whether H-2 matching is required for full cytotoxic T lymphocyte (CTL) responses to allo-H-2 antigens in allogeneic bone marrow chimeric mice. A number of irradiated, bone marrow-reconstituted chimeras constructed from various combinations of marrow cells from B10 H-2 recombinant strains and AKR recipient mice were prepared. Spleen cells obtained from such chimeras and normal control mice were activated in vitro by culturing them with irradiated stimulator cells. It was shown that spleen cells from [4R----AKR], [(4R X 3R)F1----AKR] or [AQR----AKR] chimeras, which were histocompatible on the left hand-side of the H-21 subregion between donor and recipient mice, generated greater CTL activities than those that were seen with spleen cells of [3R----AKR] or [5R----AKR] chimeras, which were histoincompatible in this region. We were unable to demonstrate suppressor cell activity of the spleen cells of [3R----AKR] chimeras cultured with stimulator cells. Although spleen cells from [3R----AKR] chimeras showed substantial proliferative responses to stimulator cells (MLR) and to Con A and LPS, IL2 activities of supernatants from Con A-activated spleen cells (Con A SN) of the chimeras were significantly lower than those of [4R----AKR] or [(4R X 3R)F1----AKR] chimeras. Furthermore, vigorous CTL activities were obtained with either spleen cells or thymocytes from [3R----AKR] chimeras when rat Con A SN was added to the MLR cultures. These observations suggest that the numbers of precursor CTLs in the cells from [3R----AKR] chimeras are at the same level as those of [(4R X 3R)F1----AKR] or normal mice and that the low CTL activities generated by spleen cells of [3R----AKR] chimeras compared to H-2I-matched chimeras are due in large measure to deficiency in IL2 production by the splenic T cells of the [3R----AKR] chimeras.

Animals↗