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K Reemtsma

Publications and source records attributed to K Reemtsma.

At least 37 records · Page 2Linked to original sources
PubMed1991

Migration patterns of dendritic cells in the rat: comparison of the effects of gamma and UV-B irradiation on the migration of dendritic cells and Lymphocytes.

To further define the underlying mechanisms of immune suppression induced by UV-B irradiation, we have examined the kinetics of homing patterns of in vitro UV-B-irradiated and gamma-irradiated-thoracic duct lymphocytes (TDL) compared to dendritic cells (DC). Our findings show that 111In-oxine-labeled TDL specifically home to the spleen, liver, lymph nodes, and bone marrow with subsequent recirculation of a large number of cells from the spleen to lymph nodes. In contrast, DC preferentially migrate to the spleen and liver with a relatively insignificant distribution to lymph nodes and an absence of subsequent recirculation. Splenectomy prior to cell injection significantly diverts the spleen-seeking DC to the liver but not to the lymph nodes, while the homing of TDL to lymph nodes is significantly increased. In vitro exposure of 111In-oxine labeled TDL to gamma irradiation does not significantly impair immediate homing to lymphoid tissues but inhibits cell recirculation between 3 and 24 hr. In contrast, gamma irradiation does not affect the tissue distribution of labeled DC, suggesting that DC are more radioresistant to gamma irradiation than TDL. Unlike the findings in animals injected with gamma-irradiated cells, UV-B irradiation virtually abolished the homing of TDL to lymph nodes and significantly reduced the homing of the spleen-seeking DC to the splenic compartment while a large number of cells were sequestered in the liver. The results of in vitro cell binding assay show that TDL, unlike DC, have the capacity to bind to high endothelial venules (HEV) within lymph node frozen sections while gamma and UV-B irradiation significantly inhibit the binding of TDL to lymph node HEV. These findings suggest that: (i) DC, unlike TDL, are unable to recirculate from blood to lymph nodes through HEV; (ii) although gamma irradiation impairs TDL recirculation, it does not affect DC tissue distribution; and (iii) UV-B irradiation impairs both TDL and DC migration patterns. We conclude that the lack of capacity of irradiated TDL to home to lymph nodes is due to damage to cell surface homing receptors and that the failure of DC to home to the lymph node microenvironment is related to the absence of HEV homing receptors on their cell surface.

Animals↗
PubMed1991

Immunomodulation of kidney and heart transplants by anti-idiotypic antibodies.

To explore the possibility that circulating HLA antigens from the graft and anti-anti-HLA (anti-idiotypic) antibodies influence the long-term survival of renal and cardiac allografts, analysis of 330 renal allograft recipients and 174 recipients of cardiac allografts was conducted. Anti-donor-HLA antibodies (Ab1) present before or after transplantation are associated with graft failure, whereas irrelevant anti-HLA antibodies had no impact on actuarial graft survival. Ab1 may be uncovered by dissociation of immune complexes and depletion of soluble antigens with monoclonal antibody-coated magnetic beads. Of the 421 sera tested from 65 heart recipients, 97 showed Ab1 before depletion and 178 after depletion; similar rise in positive sera was seen in 39 renal transplant recipients. Three distinct patterns of appearance of Ab1 and Ab2 (anti-Ab1 antibody) were recognized. Patients with cyclic variations of Ab1 in association with Ab2 had 100% graft survival, whereas patients with cyclic variations of Ab1 but no detectable Ab2 had 2-year graft survival of 36% for kidneys and 71% for hearts. Presence of Ab1 in all sera after transplantation led to 47% and 56% 2-year renal and heart allograft survival, respectively.

Actuarial Analysis↗
PubMed1991

The role of anti-HLA antibodies in heart transplantation.

The major threat to long-term survival of heart allograft recipients is the development of graft atherosclerosis, which seems to be a manifestation of chronic rejection. To assess the role of anti-HLA antibodies in heart allograft rejection we studied 107 patients and compared the survival of recipients who formed anti-HLA antibodies with the survival of recipients who developed no antibodies. At 4 years the actuarial survival was 90% in the nonproducer group and 38% in antibody-producers (P = 0.038). We further explored the possibility that HLA antigens from the injured graft are released into the circulation and can be found in the serum either free or complexed with anti-HLA antibodies. This hypothesis was confirmed by the finding that the frequency of sera containing soluble HLA antigens from the graft or immune complexes of HLA alloantigens with anti-HLA antibodies was significantly higher in patients who rejected compared with patients with successful heart allografts (P less than 0.05). Following depletion of soluble HLA antigens, anti-HLA antibodies became detectable in 53% and 74% sera obtained during the first and second year posttransplantation, respectively, from patients undergoing chronic rejection. Long-term survivors showed a significantly lower (P less than 0.001) frequency of anti-HLA antibodies in sera depleted of HLA antigens. Lastly, studies of anti-anti-HLA-A2 and A3 antibodies in recipient sera suggest that quiescence is maintained by antiidiotypic antibodies.

Antigen-Antibody Complex↗
PubMed1991

The accuracy of CT scanning in the diagnosis of abdominal and thoracoabdominal aortic aneurysms.

As CT scanning has evolved as a reliable clinical tool, the use of angiography in the diagnosis of aortic aneurysmal disease has diminished. Fewer than 25% of patients with aortic aneurysmal disease undergo aortic angiographic evaluation at our institution. A prospective clinical study was undertaken to assess the validity of this policy. One hundred patients with clinical or ultrasonographic evidence of aortic aneurysms were evaluated prospectively during the period July 1987 to December 1989. All patients underwent CT scanning as an initial evaluation. Patients were selected for angiography if they fulfilled any of the following criteria: radiographic evidence of thoracoabdominal or juxtarenal aneurysms, or horseshoe kidney; or clinical suggestion of renal artery stenosis, mesenteric arterial insufficiency, aortoiliac occlusive disease, or lower extremity aneurysmal disease. During this period 19 patients (19%) underwent both CT scanning and angiography. The indications for angiography were thoracoabdominal aneurysms (7), juxtarenal aneurysms (2), clinical evidence of mesenteric insufficiency (1) or renal insufficiency (2), evidence of lower extremity aneurysmal disease (3), or severe aortoiliac occlusive disease (4). Eighty-one patients (81%) underwent CT scanning as the only radiographic evaluation. No patient was adversely affected by elimination of angiographic evaluation. CT scanning revealed inflammatory aneurysms (4), retroaortic renal veins (2), and horseshoe kidney (1). This study suggests that most (81%) patients with aortic aneurysmal disease can be adequately evaluated by CT scanning, and that a very selective policy of angiographic evaluation is indicated.

Aged↗
PubMed1990

Immunomodulation of vascular endothelium. 1. Ultrastructural changes following ultraviolet B irradiation of peripheral veins.

Immunologic function of endothelial cells is especially important in consideration of vein allografting for arterial reconstruction and in organ allotransplantation. Ultraviolet B radiation (UVB) has previously been shown to modulate graft immunogenicity, and to alter cell surface receptor function. In this study, superficial epigastric veins were UVB irradiated with 10, 24, 40, 80, and 150 mJ/cm2 while control veins were not irradiated; all specimens were examined for endothelial ultrastructural changes. Veins were perfuse-fixed at 1, 3, 7, 14, and 28 days after irradiation, and were evaluated by transmission electron microscopy and scanning electron microscopy. Control veins had a normal appearing endothelial lining, composed of elongated, attenuated endothelial cells. Veins irradiated with more than 24 mJ/cm2 displayed injured endothelial cells characterized by altered microvilli, defects in the cell surface, and a change in cell shape. The degree of cell damage correlated closely with increasing UVB dose. At doses of 80 mJ/cm2 or greater there was moderate to severe endothelial cell separation from the underlying basement membrane and an increase in cellular lysosomes. The effects of UVB were maximal at 3 days with virtual recovery in resurfacing of all specimens with endothelium 28 days after irradiation. These data suggest that UVB has a dose-dependent effect on venous endothelium that is morphologically reversible with time. Cell membrane changes seen following exposure to UVB may contribute to altered cell surface receptor function.

Animals↗
PubMed1990

The role of CD4+ helper T cells in the destruction of microencapsulated islet xenografts in nod mice.

Islet transplants for large numbers of patients with diabetes will require xenografts. Microencapsulation is an appealing method for islet xenografting. However, graft function has been limited by a cellular reaction, particularly intense in spontaneously diabetic, NOD mice. The purpose of this study was to elucidate the mechanism of this reaction. Poly-1-lysine-alginate microcapsules containing 4000-12,000 dog or 1800-2000 rat islets were xenografted intraperitoneally into streptozotocin (SZN)-diabetic C57BL/6J and NOD mice, with or without recipient treatment with GK 1.5 (anti-CD4 monoclonal antibody) (20-30 microliters i.p. every 5 days, begun on day -7. Grafts were considered technically successful if random blood glucose (BG) was normalized (less than 150 mg/dl) within 36 hr. Graft failure was defined as BG greater than 250 mg/dl. Dog and rat islets in microcapsules normalized BG in both SZN and NOD mice within 24 hr routinely. Empty microcapsules and GK 1.5 treatments alone did not affect BG. NODs destroyed both microencapsulated dog and rat islets more rapidly than did SZN-diabetic mice (P less than .01). Graft biopsies showed an intense cellular reaction, composed of lymphocytes, macrophages and giant cells, and no viable islets. GK 1.5 treatment significantly prolonged both dog-to-NOD and rat-to-NOD grafts (P less than 0.01). Biopsies of long-term functioning grafts (on days 65-85) demonstrated viable islets and no cellular reaction around microcapsules; 1/4 rat and 1/8 dog islet xenografts continued to function indefinitely in NOD recipients, even after cessation of GK 1.5 therapy. Prediabetic NODs receiving encapsulated dog or rat islets mounted a moderate cellular reaction to grafts. Empty microcapsules excited no cellular reaction in diabetic or prediabetic NODs. We conclude that the NOD reaction to microencapsulated xenogeneic islets is helper T cell-dependent, and that the target of this reaction is not the microcapsule itself, but the donor cells within.

Animals↗
PubMed1990

Microencapsulated dog and rat islet xenografts into streptozotocin-diabetic and NOD mice.

Microencapsulation is an appealing method for islet xenografting. However, graft failure has been related to a cellular reaction, particularly intense in spontaneously diabetic, NOD mice. The goal of this study was to characterize this reaction. Poly-l-lysine-alginate microcapsules containing dog or rat islets were xenografted intraperitoneally into streptozotocin (SZN)-diabetic C57BL/6J and spontaneously diabetic NOD mice, with or without recipient treatment with GK 1.5 (anti-CD4 monoclonal antibody). Both dog and rat islets in microcapsules normalized blood glucose (BG) routinely in both SZN and NOD mice within 24 hours. Empty microcapsules and GK 1.5 treatment did not affect BG. NODs destroyed both microencapsulated dog and rat islets more rapidly than did SZN-diabetic mice (P less than 0.01). Graft biopsies showed an intense cellular reaction and no viable islets. GK 1.5 treatment significantly prolonged both dog-to-NOD and rat-to-NOD grafts (P less than 0.01). Biopsies of long-term functioning grafts (on days #70-#95) demonstrated viable islets and no cellular reaction. In prediabetic NODs, encapsulated dog and rat islets elicited a moderate cellular reaction. Empty microcapsules excited no cellular reaction in either diabetic or prediabetic NODs.

Animals↗
PubMed1990

Immunomodulation of vascular endothelium: effects of ultraviolet B irradiation on vein allograft rejection.

Prosthetic grafts of vein allografts are inadequate as small-diameter vessel substitutes. We have applied ultraviolet B (UVB) irradiation to modulate the immunogenicity of vein allografts to avoid immunologic injury. The veins of male ACI rats were irradiated with UVB (60 mJ/cm2) in situ and transplanted to male ACI rats (autografts) and female Lewis rats (allografts). Nonirradiated veins served as controls. At 4, 7, 14, and 28 days, all grafts were patent and were studied for morphologic changes by scanning electron microscopy and for immunogold labeling of major histocompatibility complex class II antigen expression. In autografts, scanning electron microscopy demonstrated minimal endothelial loss after grafting, regardless of UVB irradiation. Untreated allografts showed severe endothelial injury 4, 7, and 14 days after transplantation. UVB irradiation of veins protected allografts from injury to the endothelium and basement membrane. Major histocompatibility complex class II-positive endothelial cells were not seen in autografts but were seen in 40% of cells 4 days after transplantation in untreated allografts. UVB-treated allografts showed MHC class II antigen expression labeling of 20% of the endothelial cells. Barr body analysis demonstrated the donor origin of these endothelial cells. UVB irradiation of rat vein allografts prolongs endothelial survival while decreasing endothelial surface expression of class II antigens. These data suggest that modification of vein immunogenicity with UVB irradiation may permit functional survival of small-vessel allografts without chronic immunosuppression.

Abdomen↗
PubMed1989

Characteristics and function of suppressor T lymphocytes in immunologically unresponsive rats following pretreatment with UV-B-irradiated donor leukocytes and peritransplant cyclosporine.

Lewis rats pretreated with UV-B-irradiated donor leukocytes (UV-DL) and peritransplant cyclosporine (CsA...CsA, 20 mg/kg on days 0, +1, and +2) accepted W/F heart allografts permanently. This study of donor-specific immunologic unresponsiveness and its cellular mechanisms shows that the induction phase of unresponsiveness is partially mediated by W3/25+ T cells, while its maintenance is dependent on the presence of 0 x 8+ T cells. In vivo adoptive transfer of either splenocytes, T lymphocytes (T cells), or W3/25+ T cells from ungrafted, UV-DL-transfused rats into unmodified syngeneic Lewis rats that received test grafts 24 hr later led to significant prolongation of donor-specific graft survival. Adoptive transfer of 0 x 8+ cells did not influence donor-type (W/F) test graft rejection. Adoptive transfer of SpL, T cells and 0 x 8+ cells from UV-DL and CsA-treated recipients of W/F heart allografts at 20 or 180 days after transplantation led to significant donor-specific graft prolongation in naive syngeneic hosts, while adoptive transfer of W3/25+ cells, in this group, did not affect test graft survival. However, the adoptive transfer of SpL or of T cell subsets did not influence third-party (ACI) graft survival. In-vitro mixed lymphocyte reaction between thoracic duct lymphocytes obtained at various intervals following grafting from UV-DL and CsA treated Lewis recipients of W/F heart allografts and donor-type SpL resulted in significantly reduced reactivity by 78%, 75%, 69% (P less than 0.001) and 43% (P less than 0.02) compared with controls when responder TDL were obtained at 20, 50, 100, and 180 days after transplantation, respectively. In coculture studies, the MLR response to donor SpL was specifically suppressed by 60%, 57%, 46%, and 50% (P less than 0.01) at 20, 50, 100, and 180 days after transplantation, respectively, compared with controls. These data indicate that the induction of specific unresponsiveness to heart allografts in this model is mediated, in part, initially by the appearance in the host of specific W3/25+ cells either induced or recalled by UV-DL transfusion, and that a stable state of immunologic unresponsiveness is subsequently dependent on the presence of 0 x 8+ suppressor cells.

Animals↗
PubMed1989

The mechanism of the induction of immunologic unresponsiveness to rat cardiac allografts by recipient pretreatment with donor lymphocyte subsets.

In continuation of our studies using UV-B-irradiated DST and donor leukocyte (DL) recipient pretreatment to induce specific unresponsiveness to organ allografts, we have examined the relative contributions of splenic lymphocyte populations and T lymphocyte subsets in the induction of immunologic unresponsiveness. Our data show that enriched populations of MHC class II-positive B lymphocytes and the W3/25+ T cell subset obtained from splenic leukocytes using immunoadsorbent columns in conjunction with mAbs led to indefinite graft survival (greater than 100 days) in the Lewis-to-ACI rat cardiac allograft model. In contrast, pretreatment with T lymphocytes or the Ox8+ T subset was relatively ineffective in prolonging cardiac allograft survival. In addition, third-party (W/F) W3/25+ T cell recipient pretreatment did not influence the survival of Lewis cardiac allografts in ACI recipients, thus confirming the specificity of pretreatment with the T cell subset in graft prolongation. Furthermore, we have examined the underlying mechanisms of donor-specific unresponsiveness induced by donor spleen cells, B lymphocytes, and W3/25+ T cells using adoptive transfer assays. Serial adoptive transfer studies demonstrated the presence of 0x8+ suppressor T cells in the spleens of unresponsive recipients bearing well-functioning cardiac allografts and of serum "suppressor factors" that have the capacity for specifically prolonging donor-type test graft survival in naive syngeneic rats. Our findings suggest that the induction of specific unresponsiveness in this model is dependent on a sequential collaboration between the appearance of donor-specific serum factor(s) (humoral phase) and donor-specific suppressor T cells (cellular phase). These results may be potentially useful in planning future strategies for the induction of unresponsiveness to clinical organ allografts by immunologic manipulation of the host with MHC class II-positive B cell and CD4+ T cell clones.

Animals↗