摘要:

Chicken anti-rat lymphocyte globulin (CARLG) is a new and uniquely specific immunosuppressant for which the mechanisms of immunosuppressive action are not yet known. This study defines its in vivo therapeutic dose range and in vitro allospecificity. A dose response study, using CARLG or normal chicken globulin (NCG) as the sole immunosuppressant, was conducted in Lewis (Ag-B1) recipients of Buffalo (Ag-B6) rat cardiac allografts. Groups of Lewis recipients were treated with 175 mg of NCG per kg or 30,100,175, or 300 mg of CARLG per kg for the first 8 post-transplant days. Doses of 175 and 300 mg of CARLG per kg resulted in significantly longer(P< 0.01) prolongation of graft survival than doses of 30 and 100 mg of CARLG per kg, which were not significantly different(P> 0.05) in their ability to prolong graft survival than a dose of 175 mg of NCG per kg. In vitro and in vivo absorption studies revealed that CARLG does not contain strain-specific alloanti-body. When Lewis lymphoid cells were used to absorb, in vitro, a batch of CARLG produced with Brown Norway (Ag-B3) lymphoid cells as immunogen, all antibody activity toward Brown Norway cells as quantitated by a two-stage lymphocy-totoxicity assay was completely removed. In another experiment, a preparation of CARLG, produced using Buffalo lymphoid cells as immunogen, underwent in vivo absorption as a result of i.v. injection into Lewis rats. Serum levels of CARLG-binding activity to Lewis or Buffalo lymphoid cells were quantitated in vitro at intervals after injection by an isotopic antiglobulin assay. Lewis rat tissues were able to remove completely serum CARLG-binding activity toward Buffalo antigens. A mechanism of action for CARLG derived from these observations is proposed and discussed.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

The lymphocy to toxicity of 116 rhesus monkey alloantisera was evaluated in 92 unrelated rhesus monkeys and in 33 pedigreed rhesus families. The study was conducted using a standard complement-dependent microcytotoxicity assay. A computer-assisted x2analysis of the reactivity of these sera in unrelated monkeys generated 23 groups of highly correlated antisera. The two-locus model of the mammalian major histocompatibility complex was assumed for the monkey, and genetic criteria for RhL-A antigens were determined before study. Seventeen groups of antisera which had met these predetermined criteria in a previous study using a different random population of monkeys were confirmed in the present analysis. The remaining six groups also met these predetermined criteria, although the genetic data for two were incomplete. Of the 23 antigens defined, 12 appeared to be products of theAlocus and 11 of theBlocus. Nineteen were similar or identical to antigens previously described by us or by Balner and coworkers in The Netherlands. Two groups have not been previously described. A frequency analysis indicated that these 23 antigens represented approximately 75% of the total expression of theRhL-A-AandRhL-A-Bloci.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

In a previous study we showed that allografts of BN fetal bone, unlike allografts of adult bone, are not rejected by allogeneic recipients of the Lewis strain in spite of the existence of major histocompatibility complex (MHC) incompatibility between donors and hosts. In the present study, we analyzed the relationships existing between the host and fetal tissue that determine graft survival. We found that (1) the fetal BN graft, unlike adult grafts, induces in Lewis recipients a vigorous humoral response consisting mainly in the production of IgG antibody that seems to be directed against antigens of la-like specificities. (2) The BN rats are genetically defective in their capacity to respond to determinants and thus are not capable of producing anti-la antibodies; in accordance, Lewis fetal bone grafts are rejected by the BN recipients. (3) Chondrocytes isolated from fetal mouse bones do express la antigenic determinants. We suggest that the survival of an allogeneic fetal graft in an immunologically intact recipient depends on an active and selective immune response directed against the la components associated with the MHC on the embryonic and fetal cells. On the basis of these notions, we propose that the capacity of la determinants expressed on cells of the embryo, to elicit anti-la and IgG alloantibodies in the pregnant mother, determines the capacity of the embryo to escape rejection by the histoincompatible mother. In a previous study(1, 2)we demonstrated that one can successfully transplant orthotopically, in adult immunologically intact rats, allogeneic fetal bones derived from limbs of rat fetuses and thereby correct massive bone loss. Unlike adult-derived bone grafts, fetal bone grafts underwent processes of rapid ossification, bridging extensive bone defects and supporting the development of bone marrow. The striking conclusion from that work was that, unlike other adult allografts, the fetal bone escapes immune destruction in spite of the strong allogeneic barriers. This escape seemed puzzling in view of our observations that fetal bone grafts are not immunologically inert: we found that the tissue surrounding the allogeneic fetal bone graft became heavily infiltrated by lymphoid cells(1, 2). We had evidence that after transplantation the alloantigens of the fetal bone graft are recognized by T lymphocytes of the recipient, leading to the generation of alloantigen-specific helper T cells(1). In addition, we showed that the recipients of fetal bone grafts (unlike the recipients of adult bone) generate a high titer of specific alloantibodies. Thus, the striking resistance of fetal bone grafts to destruction and rejection by the host in spite of strong allogeneic differences contrasts with the generally accepted principles of transplantation genetics and allograft reactions. The phenomenon seemed puzzling in view of observations demonstrating that chondrocytes do express major histocompatibility antigens(3–6)in a manner similar to other cells of the body. Our aim, therefore, was to investigate the specific mechanisms involved in permitting the escape of a fetal bone allograft from rejection. This problem is of special interest because of its potential relevance to the escape of the allogeneic embryos and fetuses from destruction by the host immune system. It could then clarify aspects of fetomaternal relationships, as well as relations between an organism and its malignant tissues that carry fetal antigens.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

A nontoxic murine model has been developed in which sensitization to allogeneic platelet transfusions in adults can be prevented. This model is based upon allogeneic liver membrane (LM) induction of specific humoral tolerance to major histocompatibility alloantigens. In normal mice of the C3H background, syngeneic and H-2-incompatible congeneic platelets had at½= 15 ± 3 hr; for mice of the C57BL background, the comparablet½was 33 ± 6 hr. Platelets of C3H background transfused into C57BL background recipients, and vice versa, hadt½midway between, 24 ± 3 and 24 ± 2 hr, respectively. These data suggest genetically determined variation in normal platelet survival. In passively immunized C3H background mice, the t½was decreased to 10 ± 2 hr. In C57BL background mice actively immunized i.p. with allogeneic lymphoid cells,t½was decreased to 18 ± 4 hr. When allogeneic LM was given concomitantly with the allogeneic cells, however, sensitization to foreign H-2 antigens was blocked, and survival of both C3H and C57BL background allogeneic platelets remained normal. These data demonstrate that in this free cell allograft system LM treatment is a safe and effective method for preventing adult sensitization to allogeneic platelets.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Two thymic stromal fractions previously shown to have specific enhancing effects on anatomically distinct T cell populations were tested for their capacity to induce functionally distinct T cell subsets.Parental mice were injected with either soluble thymic fraction (STF) or insoluble thymic fraction (ITF), and their lymphoid cells were harvested 11 days later. It was shown that ITF elicited a splenic corticosensitive T cell subset endowed with enhanced graft-versus-host reaction (GVHR)-inducing capacity. On the other hand, STF increased, mainly in lymph nodes, the number of corticoresistant T cells significantly less active in GVHR. Furthemore, lymphocytes from ITF-treated parental donors could become corticoresistant with reduced GVHR activity after a 1-hr in vitro incubation with STF.We have thus shown that two different elements of the thymic microenvironment could modulate the intensity of the GVHR by modifying the equilibrium between two T cell subsets. These are believed to represent two consecutive differentiation stages.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Sequential sections were prepared from isografted or allografted sciatic nerves in adult female DBA/2 mice and were compared with the wallerian degeneration in the same inbred strain. Transverse sections were studied by qualitative and quantitative histology. Rejection was manifested by an important infiltration of mononuclear cells, including large pyroni-nophilic cells, around the grafted nerve, followed by the appearance of irregular infiltrates around the neovessels within the nerve. In parallel, the number of endoneural nuclei increased less rapidly in allografts than in isografts up to day 15 and diminished thereafter, in association with a possible reduction of neural vascularisation.The results of nerve grafting in clinical cases are extremely difficult to assess because of the various origins of the grafts, the diversity of the preservation techniques, and the varying standards adopted for estimating recovery. Although peripheral nerves are quite likely to elicit an immunological rejection reaction when transplanted into an allogeneic host, as do most other tissues, very little is yet known of the mechanisms and functional or histological manifestations of this reaction. Hence, despite many attempts at conditioning peripheral nerves to minimise immunological rejection, the distinction between technical and immunological failures often remains impossible (1–4). A better knowledge of the rejection of peripheral nerves appears critical if the recent developments of transplantation immunology (e.g., tissue typing, host conditioning) can be applied to nerve grafting in clinical situations. The major difficulty in analysing the histological changes associated with nerve allograft rejection is the presence of the wallerian degeneration reaction of the graft which consists of a proliferative process of different kinds of cells including, in addition to Schwann cells, macrophages, and fibrocytes (5, 6).We report here the sequential study of tissue sections of sciatic nerves grafted into inbred allogeneic mice compared with syngeneic grafts performed in the same recipient. Both allografts and isografts were compared with the wallerian degeneration obtained by section of the sciatic nerve in mice of the same inbred strain. The histology of the immunological rejection reaction could therefore be defined on quantitative grounds.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Seven murine anti-H-2 and three nonimmune mouse sera were tested for cytotoxicity toward B and T lymphocytes from a panel of human donors. One group of sera, including two anti-H-2.33 sera, exhibited cytotoxicity directed exclusively toward human B but not T cells from all donors. Absorption studies on human lymphoblastoid cell lines (LCLs) of B or T cell origin corroborated these findings. Some nonimmune sera showed similar characteristics, indicating that the observed reactions were not attributable to cross-reactivities between mouse H-2K or D specificities and human antigens coded by theHLA-A, B,orClocus. Another set of mouse sera (anti-H-2.28b and anti-H-2.31) was highly cytotoxic to both B and T cells of some donors but not of others, suggesting that activity in these sera may arise from cross-reactions between mouse and human specificities. A third set of anti-H-2 as well as normal mouse sera showed only background cytotoxicity when tested on human cells.The ability of the B cell cytotoxic mouse sera to block the human mixed lymphocyte culture reaction (MLR) was compared to that of appropriate human alloantisera with exclusive B cell activity or a rabbit serum raised against human B cells. None of the mouse sera resulted in a significant reduction in the human MLR, whereas the human alloantisera as well as the rabbit antiserum caused a significant amount of blocking at several dilutions beyond their highest cytolytic titer.In an extensive search for cross-reactivity between specificities of the mouse and human major histocompatibility complex (MHC), Ivaskova et al. (1) found that many congenic H-2 sera react with almost all human cells if the serum dilutions are sufficiently low. Associations between someHLAlocus antigens (mainly A2, B7, and B27) and certain of the H-2 sera can reportedly be detected only when end point titrations are carried out. The authors point out that there is considerable variability in the strength of reactions of human cells with the mouse alloantisera and that reproducibility of typings is not as good as with HLA alloantisera. This may indicate that some of the antibodies in the H-2 antisera may actually be reacting with subpopulations of human lymphocytes. The proportions of B and T cells from different donors seem to vary from bleed to bleed. This variability could result in different end titration points in sera containing mostly B cell antibodies. The reactivity of the HLA specificities with well defined typing sera usually varies little. This is to be expected, since HLA antigens are present on all lymphocytes. Therefore, some of the differences in reaction strengths observed when donors carrying similar HLA antigens are tested with heterologous antisera may be attributable to reactions involving only certain lymphocyte subpopulations.A preliminary investigation in this laboratory indicated that human LCLs, with B cell characteristics are much more sensitive to H-2 alloantisera than those classified as T cells. The present study demonstrates that some mouse sera exhibit cytotoxic patterns toward separated human B and T cells that closely resemble those of xenoantibodies produced against human B cell lines. The effect of the mouse sera on the human MLR is also investigated. The blocking activity of the mouse sera is, however, much weaker than that of xenoantibodies or human alloantibodies recognizing DRw specificities.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

The phagocytic and metabolic functions of the reticuloendothelial system (RES) were determined, by measuring the plasma clearance rate of125I-labelled microaggregated human serum albumin and the increase in plasma metabolites of this test substance, in patients with chronic renal failure and in renal transplant recipients at different times after transplantation. All transplant recipients received triple immunosuppressive therapy consisting of azathioprine, corticosteroids, and antilymphocyte globulin. The intravascular clearance of microaggregated albumin was significantly depressed in patients when tested at 1 to 12 days(P< 0.001), 1 to 4 months(P< 0.02), and 6 to 9 months(P< 0.001) after transplantation compared to pretransplantation. The 1− to 3-year transplant survivors had a normal RES phagocytosis. Furthermore, the metabolic RES function in all groups of transplant recipients except the group of patients tested at 1 to 4 months after transplantation was significantly impaired compared to pretransplantation.Administration of antilymphocyte globulin and extremely high daily doses of steroids were probably responsible for the significant depression in the RES functions recorded immediately post-transplantation. The further development of the phagocytic ability of the RES was shown to be correlated to the cumulative dose of steroids given over the last 12 months. The azathioprine regime seemed to have no influence on the RES functions.The RES is a major host defence mechanism against bacterial and viral infections(1–4)and tumour growth(5–7). Macrophage phagocytosis and metabolism are also important in the induction of an immune response to foreign antigens(8–10)and in the rejection of allografts(11, 12). Depression of the RES function induced by various agents (methyl palmitate, trypan blue, silica, carrageenan, or antimacrophage serum) was shown to prolong the survival of organ as well as tumour grafts(13–17). On the other hand, glucan-induced stimulation of the RES was associated with enhanced rejection of both tumour and bone marrow transplants(14, 17).Immunosuppressive agents such as azathioprine, corticosteroids, and antilymphocyte serum, used in transplantation surgery to suppress the immune response, have been reported to impair RES phagocytosis(18–21). Several investigations have been made in animals and some in man on the capacity of the RES to clear various colloids and lipid emulsions from the circulation(22–25). In recent years, moreover, methods have been developed for the determination of not only the phagocytic but also the metabolic function of the RES(26–28). Those used most frequently utilize a rapidly metabolizable RES test substance of microaggregated human serum albumin labelled with radioactive iodine, a substance which can safely be used in man(26, 28).The purpose of the present study was to determine both the phagocytic and the metabolic functions of the RES in patients undergoing renal transplantation during immunosuppressive therapy. As RES test substance, microaggregated human serum albumin labelled with125I was used.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Human endothelial cells were separated by collagenase digestion from the umbilical vein of newborns. The cytotoxic effect of antisera against HLA-DRw antigens was tested on monolayers of endothelial cells, using a51Cr retention microcytotox-icity assay in the presence of rabbit complement. Of the endothelial monolayers tested, significant concordance between the typing results obtained using cord blood-derived B lymphocytes and endothelial cell monolayers was observed. A rabbit anti-human polyspecific B cell antiserum was also capable of completely lysing the endothelial monolayers tested. In addition,5ICr-labelled dissociated endothelial cells were lysed by nonimmune peripheral blood mononuclear cells in the presence of DRw antisera having a specificity for the target endothelium.The vascular network of allografted organs is an important site for immunological injury and endothelial damage is a common histopathological observation in both acute and chronic rejection. Although the mechanism of allograft vascular destruction is presently incompletely understood, damage to endothelial cells in vitro by antibodies via complement-dependent or cell-mediated cytotoxicity has been demonstrated(1–3).Although all nucleated cells carry the HLA-A, B, and C antigens, the tissue distribution of the HLA-DRw antigens appears to be limited primarily to B lymphocytes, monocytes, epidermal Langerhans cells, and possibly sperm (see Ref.(4)). We present evidence here that human endothelial cells also carry the DRw antigens similar or identical to those expressed on human B cells and monocytes, and that anti-DRw antisera in the presence of complement are capable of specifically destroying monolayers of human endothelial cells. In addition, we also describe damage to dissociated human endothelial cells in vitro by nonimmune allogeneic peripheral blood mononuclear cells in the presence of anti-HLA-A, B, or DRw antibodies. A preliminary report describing part of our studies will appear elsewhere (5).

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Transplantation immunity was examined in mouse H-2− and non-H-2-disparate strain combinations by the macrophage electrophoretic mobility (MEM) assay. Lymph node cells from the recipients rejecting histoincompatible skin grafts were incubated in the presence of solubilized histocompatibility antigens prepared from spleens of the graft donors. Product(s) of lymphocyte-antigen interaction in appropriate combinations (sensitized lymphocytes with the sensitizing antigen) significantly diminished the electrophoretic mobility of guinea pig macrophages in all of the histoincompatible strain combinations examined. The data indicate that transplantation immunity in mice can be detected by the MEM assay.

ISSN:0041-1337    

出版商:OVID    

年代:1979

数据来源: OVID