ISSN:0041-1337    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

SUMMARYThe immunosuppressive effects of methylprednisolone (MP) (5 mg/kg) and cyclophosphamide (CY, 180 and 48 mg/kg) on cellular immune responses to allogeneic tumor cells were evaluated using in vitro tests. The variations in the number of splenocytes and the in vivo response to the injection of allogeneic tumor cells (rejection or facilitation) were recorded. The drugs were administered at different times in relation to immunization. Polyclonal stimulation essentially reflected T cell recovery, whereas monoclonal stimulation was depressed when the drugs were administered at the time of immunization, suggesting a defect at the level of sensitization. MP had little effect on cytotoxicity but was nevertheless associated with allograft facilitation. CY however strongly inhibited the specific activity of cytotoxic lymphocytes when administered at the time of inoculation, but this was associated with normal graft rejection. Reduced numbers of T cells and increased cytotoxicity was recorded when both drugs were administered 2 days prior to immunization. Thus, this study (1) has shown that MP-induced facilitation does not correlate with the levels of in vitro cytotoxicity; (2) has demonstrated a dissociation of the effect of CY on in vitro cytotoxicity and the in vivo response when given at the time of immunization; and (3) confirmed the hypothesis that CY enhances T cell responses when given 2 days before immunization and similar observations being extended to MP treatment. It also suggested that the cytotoxicity observed at that time was responsible for graft rejection.Methylprednisolone (MP) and cyclophosphamide (CY) are widely used as immunosuppressors to induce graft acceptance. Cytotoxic lymphocytes (CTL) are thought to be responsible for graft rejection because they express lytic activity against H-2-incompatible cells (7). However, other components of the immune system play an important role in allograft rejection and facilitation. In particular, B cells and antibodies that may have either cytotoxic or enhancing effects mediated through different mechanisms such as the protection of target cells from cytotoxic effectors (16) or in provoking the formation of antigen-antibody complexes, “defusing” CTL from their targets (24). Suppressor T cells may also participate in graft facilitation and they may be present as such or may be induced by the presence of antigen-antibody complexes (12). However, because of the strong relationship between cytotoxicity and allograft rejection, we wanted to verify whether these immunosuppressive drugs had any effect on the T cell population as evaluated by nonspecific tests (polyclonal stimulation) and specific tests (mixed lymphocyte cultures (MLC) and chromium release test) and to correlate this effect with in vivo graft rejection.

ISSN:0041-1337    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

SUMMARYA standardized procedure is proposed for deliberate immunizations against human major histocompatibility complex determinants. The data presented demonstrate its effectiveness and, by using a number of necessary precautions, this procedure has proven to be very safe. The following points are especially important: (1) exclusive utilization of regular blood donors as immunizers; (2) use of whole blood as an immunizing agent; and (3) use of small immunizing stimuli rather than large transfusions. This procedure can be recommended for the production of monospecific anti-HLA antisera and it may be useful if and when a deliberate transfusion policy for prospective kidney recipients is adopted.Because of the increasing complexity of the HLA system, planned immunizations become more and more necessary if extensive selections and absorptions of sera from multiparous women are to be avoided. Also, there is evidence indicating the beneficial effect of blood transfusion on the outcome of kidney transplants (1–5). This may create in the future the requirement for deliberate transfusion also in these cases.A standardized immunization procedure in volunteer recipients has been undertaken by our group during the past 9 years. Based on the considerable amount of data collected, we can confidently recommend this procedure as both safe and effective in eliciting anti-HLA antibodies.

ISSN:0041-1337    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

SUMMARYThe expression of immune response-associated (la) antigens on the surface of mouse strain GR (H-2dx) ascites leukemia (GRSL) cell lines was studied by cytotoxic tests, immunofluo-rescence, and immunoprecipitation assays. la expression varied among the three GRSL cells lines (GRSL 2, GRSL 14, and GRSL 15) studied by cytotoxic assay. GRSL 14 cells showed the strongest expression of la antigens among these three cell lines. A time-course study of tumor growth in mice revealed that Ia antigens on the tumor cells demonstrated the strongest expression 10 days after injection of GRSL cells into GR mice, and that subsequently it decreased until the death of the animal. Cells treated with neuraminidase exhibited more readily detectable la antigens, especially in the late stages of leukemia, which suggested that la antigens had been masked by sialic acid. Immunoprecipitation studies revealed that Ia molecules on the leukemia cell had the same molecular weight as those on the normal lymphocytes. Immunofluorescence studies disclosed that la antigens were distributed diffusely on the surface of the tumor cells.The I (immune response) region of the mouse major histo-compatibility complex codes for gene(s) controlling a series of lymphocyte membrane alloantigens (la) and many immunologically related functions, including genetically controlled immune response (2, 22), graft-versus-host reactivity (16), and mixed lymphocyte reactivity (1). Ia determinants are expressed principally on lymphocytes but also are found on macrophages, sperm, and epidermal cells (12). Although during the period when Ia antigens initially were being described there was some controversy about the expression of Ia determinants on T cells (9, 11, 20), currently, there is unanimous agreement that la antigens are expressed on at least a subset of T cells as well as on most B cells (6, 10). I region determinants expressed exclusively on T cell subpopulations also have been described (17, 23).Previous studies on tumor cells by direct cytotoxic assays suggested some expression of la antigens, but results of absorption testing were negative (David, unpublished data). Tumor cell line S1 (BALB/c, H-2d), a lymphocytic lymphoma, was shown to be positive for Ia.7 by both direct tests and absorption analyses (5). Further characterization of Ia antigens on these tumor cells, however, became very difficult because of interference by murine leukemia virus (MuLV) antigens that are expressed on these cells and detected by the alloantisera, which contain anti-MuLV antibodies on almost all cases. Screening of several AKR (H-2k) thymomas also revealed reactivity caused by MuLV antigens (25).In these studies, we used lymphatic leukemia cells maintained as ascites cells in the strain GR (H-2dx), which has a high incidence of mammary cancer and an incidence of about 20% thymic lymphomas in male mice. GR ascites leukemia (GRSL) cells have the advantage that they lack detectable MuLV antigen (13), although the Gix antigen is present (14). Furthermore, these cells have been characterized extensively for other cell surface markers (15), which would be of value in ascertaining their relationship to la antigen.We tested to see whether all of the individual Ia specificities expressed on normal GR strain lymphocytes are expressed also on GRSL tumor cells. For further confirmation of the expression of Ia antigens on the surface of tumor, immunoprecipitation assays and immunofluorescence techniques were also used.

ISSN:0041-1337    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

SUMMARYBone marrow removed from leukemic patients during remission, for retransplantation during relapse, may contain residual leukemic cells. Antisera against surface antigens of these cells should not react with hemopoietic stem cells. In order to produce an appropriate antiserum, rabbits were given injections of cells from the common form of acute lymphoblastic leukemia (cALL) of childhood. The resultant antiserum was absorbed with liver-kidney homogenate, chronic lymphoid leukemia cells (CLL), normal peripheral lymphocytes, and lymphoblastoid cells from B cell lines. The purified globulin fraction showed high complement-dependent cytotoxicity against the cells of 39 of 56 patients with ALL. It did not react with the cells of 11 T-ALL, 1 B-ALL, and 5 undifferentiated (without known markers) ALL. Furthermore, the antiserum did not react with the cells from acute myeloid leukemias, chronic lymphoid leukemias, B-type lymphoblastoid cell lines, normal bone marrow cells, and peripheral blood lymphocytes. Unabsorbed anti-cALL globulin was found to be highly cytotoxic against hemopoietic colony-forming cells (CFU-c) and completely inhibited the growth of marrow cells and CFU-c in diffusion chambers. Absorption of anti-cALL with liver-kidney homogenate, CLL, and peripheral blood lymphocytes removed only part of the cytotoxic antibodies cross-reacting with antigens present on CFU-c. An additional absorption with lymphoblastoid cell lines removed the cytotoxic effect of anti-cALL against CFU-c completely and did not inhibit proliferation of marrow cells and CFU-c in diffusion chambers, while high cytotoxicity against cALL blasts was preserved.It follows that cALL antiserum lacks an inhibitory effect on normal hemopoietic stem cells when measured in CFU-c and diffusion chamber assays.The nonreactivity of cALL antiserum against hemopoietic stem cells would be a prerequisite for a therapeutic use of the antiserum in “antileukemic auto transplantation”. This is an approach to eliminate by antibodies against cell surface antigens residual leukemic cells in the bone marrow taken during remission and stored for retransplantation in relapse. Its principle was tested in a previous study on mice, where anti-T cell globulin was shown to eradicate leukemic cells without inhibiting stem cells required for bone marrow transplantation (25).In this study the question was raised whether anti-cALL made specific against common ALL (27), affects normal hemopoietic stem or precursor cells. The inhibition of colony-forming cells was used to test for a possible cytotoxic or inhibitory effect of the antiserum (18). This system was applied along with the diffusion chamber technique as an indicator for stem cell function.

ISSN:0041-1337    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

SUMMARYThe potential of cells from the Peyer's patches (PP) of normal adult DBA/2 Tru mice (DBA/2) to induce a graft-versus-host reaction when injected into (C57BL/6 Tru × DBA/2 Tru)F1hybrid (B6D2F1) mice was studied. The injection of 106to 107DBA/2 PP or spleen cells i.p. into neonatal F1mice produced a striking splenomegaly. Comparable doses of parental PP or spleen cells injected into a rear footpad of adult F1mice also induced a marked enlargement of the draining popliteal lymph node. In addition, PP cells were also capable of producing a lethal runting syndrome when injected i.v. into sublethally irradiated adult F1recipients. In all assays, injection of synge-neic B6D2F1cells had little or no effect. Treatment of the DBA/2 PP cells with anti-&thetas; serum and complement abolished their capacity to induce splenomegaly in neonatal F1mice. The graft-versus-host reaction activity of the PP cells could also be eliminated by thymus deprivation of the donor DBA/2 mice. These data are contradictory to previous findings in which it was observed that mouse PP cells were unable to induce graft-versus-host reaction.There is now considerable evidence demonstrating that the Peyer's patches (PP) of the small intestine contain T cells. For example, in the mouse some 20 to 40% of the cells in the PP display the &thetas; antigen on their surface (1), and, in addition, neonatal thymectomy considerably depletes the lymphocyte populations of the interfollicular zones (2). Several groups of workers have attempted to delineate the functional characteristics of PP T cells. It has been shown in vitro that mouse PP cells display helper activity in the antibody response to sheep red blood cells, can be primed for cell-mediated cytotoxicity against allogeneic target cells, and can be carrier primed by antigen feeding (3, 4). However, in order to mediate these functions in vitro, accessory adherent cells from another source must be added to the culture system, suggesting that in the mouse PP, a macrophage-like accessory cell is functionally absent. The potential to induce a graft-versus-host reaction (GVHR) is yet another feature of mature T cells, but there is conflicting evidence on the capability of PP cells to produce this effect when injected into the appropriate recipients. Earlier studies demonstrated that PP cells from both mice and rats were unable to induce GVHR (5–7) and, furthermore, were also unable to produce the allogeneic effect (8). In contrast, the work of Levin et al. (9) conclusively showed that in the rat and guinea pig, PP cells could not only induce a GVHR but could also participate in the mixed lymphocyte reaction and release a lymphocyte-derived chemotactic factor. In the mouse, however, the possibility still exists that as well as lacking a functional macrophage-like accessory cell, PP also lack T cells capable of inducing a GVHR in vivo.This study was therefore undertaken to determine, using several in vivo assays, whether mouse PP contained cells capable of inducing a GVHR. The results presented will clearly show that such a cell type is indeed present in the mouse PP, and that its functional capacity is dependent upon the presence of an intact thymus in the donor animal. Also, treatment of PP cell suspensions with anti-&thetas; serum and complement abolishes their ability to mount a GVHR.

ISSN:0041-1337    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

SUMMARYA new colloid hyperosmolar solution with high concentrations of proteins, potassium, and glucose has been favorably compared with a crystalloid, intracellular, and hyperosmolar solution (Sacks II) for 24-hr hypothermic storage of ischemic and nonischemic canine kidneys. Sixty minutes of warm ischemia was overcome by all kidneys flushed with the colloid hyperosmolar solution. In four of six ischemic kidneys flushed with Sacks' solution the function returned to normal limits. Hypothermic storage (24 hr) without warm ischemia did not cause any deleterious effects on either one of the flushed group of kidneys. Thirty minutes of warm ischemia followed by 24-hr hypothermic storage was tolerated by most of the kidneys (83%) flushed with the colloid hyperosmolar solution and one-half of the kidneys flushed with the crystalloid hyperosmolar solution. Sixty minutes of warm ischemia and 24-hr hypothermic storage was detrimental to 50% of the kidneys flushed with the colloid hyperosmolar solution.Hypothermic storage is a less expensive method for preserving kidneys for short periods of time. There are basically two solutions in current use for kidney hypothermic storage: Collins' solution (3–5) with high normal osmolarity and intracellular composition, and Sacks' solution (12), hyperosmolar with intracellular concentration of electrolytes. This paper compares the effectiveness of Sacks' solution and a new colloid hyperosmolar solution for 24-hr hypothermic storage of ischemic and nonis-chemic kidneys.

ISSN:0041-1337    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

SUMMARYNine patients with adult acute leukemia were treated in relapse with piperazinedione plus supralethal total body irradiation in conjunction with autologous marrow infusion. Bone marrow cells were collected and stored in first remission. Storage time varied from 3 to 23 months. Before storage, marrow cells were separated using density albumin gradients in order to reduce the number of leukemic cells in the graft. Three patients died before day 14 after transplantation because of complications already present at the time of transplantation. In six patients, hemopoietic recovery started to occur within 14 days after transplantation. In four patients leukemia-free periods were obtained, lasting 60+ days. The three patients with the longest leukemia-free period after transplantation (range 75 to 220+ days) are reported in more detail. One patient is still alive without evidence of leukemia, with full hematological recovery 220+ days after transplantation.Recently progress has been made in increasing rates of remission in adult acute leukemia using combination chemotherapy, but only 25 to 30% of the patients survive for 2 years or longer (1). Allogeneic bone marrow transplantation, using HLA-identical mixed leukocyte culture-negative related donors in combination with chemotherapy and total body irradiation (TBI), has been used as therapy in relapsed leukemia patients. Allogeneic marrow transplantation, however, is limited to only 25% of relapsed leukemia patients because of the low frequency of compatible marrow donors. Autologous bone marrow cells collected in remission may offer an alternative to allogeneic marrow cells for transplantation in relapse. In this paper we report the overall results of nine patients, and more specifically the data of three patients with adult acute leukemia who were treated at the time of relapse with high-dose chemotherapy and TBI, followed by autologous marrow infusion. The marrow cells to be used for transplantation were collected and subsequently stored in first or second remission. The patients were grafted in relapse when chemotherapy alone failed to induce a remission. In order to reduce the number of transplanted leukemia cells in the graft, the bone marrow cell suspensions were fractionated using discontinuous albumin density gradients before storage (2).

ISSN:0041-1337    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

SUMMARYA patient with congenital generalized lipodystrophy developed nephrotic syndrome with progressive renal glomerulosclerosis attributed to diabetic nephropathy.Renal transplantation was performed and the patient was discharged with normal renal function. Marked hyperlipidemia (17,500 mg/dl) persisted. One month later renal malfunction developed, and an open renal biopsy was performed when there was no response to antirejection therapy. Massive lipid deposition in renal tubular cells with tubular necrosis and hemorrhage was present but only minimal evidence of graft rejection. Rejection therapy was tapered and renal function stabilized. Death occurred 2 months later because of pulmonary sepsis.Patients with generalized lipodystrophy and severe hyperlipidemia may be at an unusually high risk for renal homograft destruction.Generalized lipodystrophy is a rare disorder of obscure etiology that may be congenital or acquired. The two forms are similar in that both have total absence of fat, hepatomegaly with cirrhosis, and hyperlipidemia. However, there are features that distinguish the two forms. The congenital variety, having its onset at birth (3) with equal sex distribution (1), is associated with diabetes mellitus only in the later stages of the disease. Also frequently present in the congenital variety are accelerated growth (15) and acanthosis nigricans, (12, 13). The acquired form presents later in life, has a female sex predominance, and is usually associated with diabetes mellitus from the onset (16). There is no evidence that the acquired form is inherited, whereas the congenital variety seems to be inherited as an autosomal recessive trait (11, 17). The term lipoatrophic diabetes characterizes patients that have generalized lipodystrophy associated with diabetes mellitus. The entire clinical syndrome of lipoatrophic diabetes as first described by Lawrence (6) encompasses: (1) generalized lipodystrophy (complete absence of subcutaneous, intra-abdominal, and perinephric fat); (2) hepatosplenomegaly; (3) insulin-resistant diabetes with little tendency to develop ketosis; (4) hyperlipidemia; and (5) a marked elevation of basal metabolic rate without other evidence of hyperthyroidism.Although renal involvement has been reported in patients with lipoatrophic diabetes, renal failure has not been a common occurrence. Hepatic failure secondary to cirrhosis occurs frequently and is the most common cause of death in these patients (11). Hemorrhage from esophageal varices has been a frequent complicating factor (16).We wish to report observations made of a patient with lipoatrophic diabetes and chronic renal failure. The renal failure in this patient necessitated hemodialysis and eventually cadaveric renal transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

SUMMARYVisceral yolk sac displaced outside the uterus after fetectomy differentiates into benign teratomas. This differentiation only occurs in a syngeneic pregnancy but never in hybrid pregnancy. Hybrid teratomas, however, were obtained after the induction of active or passive immunological enhancement. These hybrid teratomas, although smaller than the syngeneic, contained tissues derived from the three germ layers.Immunological enhancement, both active (antigen-mediated) and passive, was first demonstrated with tumor allografts (3). Prolonged survival attributable to enhancement was further described for allografts of the skin, heart, kidney, and various other normal adult tissues. From these results it became obvious that allograft survival varied greatly in relation to the kind of adult organ transplanted (5). Comparative studies on allograft survival of different organs, however, requires a high degree of surgical skill and are technically not feasible for all organs and tissues. Therefore, in this study, we used the previously described model of yolk sac-derived rat teratomas. These teratomas are easy to induce and contain well-differentiated tissues, derived from all three germ layers ( 7–9). They develop only in an intrastrain, never in an interstrain pregnancy. This is probably because of the presence in the yolk sac of histocom-patibility antigens of paternal origin, which are foreign to the host and lead to the immunological rejection of this extrauterine-displaced membrane. It is now well known that female mice of one inbred strain, pregnant by males of another strain, accept tumors that are genetically related to the males. Similar results have been obtained with paternal skin grafts, which survive in the mother during hybrid pregnancy for periods longer than the usual survival times of unrelated skin grafts (1). Furthermore, that this applies also to fetal tissue is illustrated by our results on the protective effect afforded by an interstrain pregnancy on the development of allogeneic blastocysts (12).Since it is known that antidonor serum injected into the recipient can enhance the allogeneic transplant (4, 6, 10, 11), we attempted to establish whether the development of hybrid teratomas could also be facilitated by the antipaternal antibodies.

ISSN:0041-1337    

出版商:OVID    

年代:1978

数据来源: OVID