摘要:

In this study delayed-type hypersensitivity against histocompatibility antigens in mice was suppressed by a single donor-specific blood transfusion. Whole blood as well as purified white blood cells and purified red blood cells were capable of inducing suppression. White cells appeared more potent in inducing suppression than red cells. Suppression was dose-dependent, still detectable after administration of as little as 0.001 ml of whole blood and maximal at a dose of 0.1 ml. The suppression was already present a few hours after transfusion and proved to be long-lasting. The suppressive effect could be transferred to naive recipients by Thy-1+,L3T4−,Lyt-2−spleen cells. This suppressor T cell population was of recipient origin—which excludes the possible involvement of “veto cells” and suppresses the afferent phase as well as the efferent phase of the DTH response.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The flow cytometric crossmatch (FCXM) has become an increasingly utilized method to detect low levels of anti-donor antibodies (e.g., anti-HLA) in potential renal allograft recipients. Anti-donor antibodies not apparent in the standard complement-dependent crossmatch, but detectable by the FCXM, are often associated with increased episodes of graft rejection and early graft failure. In this study we examined several parameters of the FCXM in order to establish a standardized methodology. First, we observed that optimal staining results were obtained when the secondary antibody was an Fc-specific, F(ab')2anti-human IgG. In contrast to an anti-whole immunoglobulin antibody, the anti-Fc specific reagent did not react with surface immunoglobulin on B cells but was reactive with cytophilic immunoglobulin present on CD 16+cells. Next we determined that dual-color analysis was superior to single-color analysis both for the evaluation of T cell reactivities and for the discrimination of T cell from B cell reactivities. Additionally, dual-color analysis revealed that the density of class I histocompatibility antigens on B cells is greater than on T cells, indicating that B cells may be a more sensitive target for detecting low levels of anti-class I antibodies. Finally, we determined that a shift in the mean fluorescence intensity of >10 channels on a 256-channel, 3-decade log scale was indicative of a positive FCXM. The data presented in these studies provide the basis for performing standardized dual-color FCXM with increased sensitivity and specificity.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Until recently, the transplantation of skeletal muscle across a major histocompatibility barrier has proved difficult. However, with the advent of cyclosporine (CsA), it has become possible to achieve extended survival across such histocompatibility barriers. To date, very little is known about the histochemical, biochemical, immunological or contractile properties of longterm-surviving muscle allografts. Consequently, it was the focus of this study to histochemically examine muscle allografts prolonged with CsA and determine the cross-sectional area of fast glycolytic muscle fibers. Measurements of cross-sectional area were made because they are an important correlate to the amount of tension a muscle can generate. Animals were assigned randomly to one of three groups: control (normal) (n = 5), syngeneic (n = 4), and allogeneic (n = 4). Muscle allografts were performed by transplanting the gastrocnemius of an ACI rat (RTla) hindlimb into the hindlimb of a Lewis rat (LEW;RT11). The syngeneic model consisted of an ACI-to-ACI transplant. Animals in the allograft group were given CsA (8 mg/kg/day) until the time of sacrifice. At approximately 100 days following transplantation,

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Rejection of H-2 class I bm 1 mutant skin allografts by B6 recipient mice is mediated by a population of CD8+anti-bm1 cytotoxic T-lymphocytes that produces and consumes its own T helper factor in response to bm1 skin allografts (dual function CTL).Previously we have demonstrated that transfusion of allogeneic lymphocytes across an H‐2 class I disparity induces specific long‐lasting skin allograft survival.We now show that intravenous injection of allogeneic spleen cells across the bml mutant disparity results in a temporary decrease of donor‐reactive CTLp in the spleen of recipient mice, lasting for approximately five weeks. The sponge matrix allograft model was used to show that allograft tolerance is caused by a specific functional clonal deletion of CTLp within the allograft. We propose that dual function CTL are vetoed by donor T cells, resulting in skin allograft tolerance.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

From an immunologic viewpoint, the fetus with its paternal antigens may be considered a successful allograft in the maternal host. Understanding the basis of this host-allograft relationship remains a fundamental unsolved problem in transplantation immunobiology. We have previously demonstrated that local immunoregulation in the murine placenta prevented macrophage activities necessary for an effective response against the intracellular bacteriumListeria monocytogenes. Given the central role of macrophages both as antigen-presenting and cytolytic effector cells, such local immuno-regulation may ordinarily help prevent rejection of the fetoplacental unit with its paternal alloantigens by the maternal immune system. We therefore examined two types of interaction between macrophages and the placental cells that populate the maternal-fetal interface. (1) Upon activation to kill listeria efficiently, macrophages also acquire cytolytic capacities against some tumor and embryonic cells. We tested the hypothesis that macrophage activation in the placenta was inhibited to prevent macrophages from lysing fetal tropho-blasts. We found, however, that trophoblasts isolated by dispase dispersion, differential isopyknic centrifugation, and adherence were not lysed by three different populations of cytolytic macrophages: (a) those activated in vivo during listeriosis, (b) peptone-elicited macrophages activated in vitro by recombinant interferon gamma and other lymphokines, and (c) the macrophage cell line RAW 264.7 activated in vitro. (2) Previous studies had demonstrated that cells from the placental region and their conditioned media inhibited a variety of lymphocyte functions. However, we found that these did not inhibit activation of adherent macrophages as assessed by induction of cell-surface Ia and acquisition of tumoricidal activity. In addition, under conditions where placental cells inhibited the proliferative response of a cloned CD4+anti-ListeriaT cell line to fixed, antigen-pulsed macrophages, the secretion of macrophage-activating lymphokines was not affected. These studies are important because they indicate that previously described suppressor systems in the murine placental region do not account for the profound local deficits in macrophage function seen during listeriosis.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

In vivo cell-mediated effector mechanisms of allograft destruction were investigated in a canine single-lung transplantation model. This large animal model permits direct longitudinal studies of immune effector cells from the grafts of individual recipients by bronchoalveolar lavage (BAL). Evidence was obtained that two types of cytolytic lymphocytes act as effectors of allograft destruction. Typical allospecific cytolytic T lymphocytes, were detected late in the course of rejection in nonimmunosuppressed recipients and in cyclosporine-treated recipients during the latter stage of drug tapering. The other type of intragraft cytolytic lymphocyte was observed in the early stages of CsA dose tapering and was characterized by ability to lyse xenogeneic targets in a lectin-dependent cytotoxicity assay but inability to kill allogeneic target cells from the lung donor. These cytolytic cells were also detected in the initial stage of lung rejection in non immunosuppressed recipients and in the early period (3 days) of mixed lymphocyte culture. Current interpretation of these data is that these latter effector cells have the characteristics of IL-2-activated killer cells (IAK). Substantial delays in the detection of intragraft donor-specific CTL relative to IAK activity were observed in recipients undergoing CsA dose tapering compared with nonimmunosuppressed recipients. This finding suggests that appropriate CsA treatment may lead to prolonged inhibition of the generation of donor-specific CTL compared with induction of IAK activity. Delayed detection of intragraft donor-specific CTL paralleled the absence of such activity in donor-specific MLC of tolerant lung allograft recipients. The result of CsA therapy may, therefore, be characterized as a state of “partial unresponsiveness,” since certain pathways of immune effector activity remain intact after termination of treatment. The differential effect of CsA on various pathways of allograft destruction may have important implications regarding concepts of alloreactivity and T cell-mediated immune responses.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID