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Biomedical subjects

D D Sedmak

Publications and source records attributed to D D Sedmak.

At least 55 records · Page 3Linked to original sources
PubMed1996

Prevalence of hepatitis C in patients with idiopathic glomerulopathies in native and transplant kidneys.

Previous studies suggest that there is an association between hepatitis C (HCV) infection and glomerular diseases in native and transplanted kidneys. However, the data are controversial. To reexamine this issue, we determined the prevalence of serum anti-HCV antibodies in patients with glomerulopathies of native kidneys (n = 105) and in patients with acute and chronic transplant glomerulopathy (TxGN) (n = 62). Compared with a control group of patients with diabetic nephropathy (n = 37, 0% HCV+), the prevalence of HCV antibodies was significantly higher in patients with focal glomerulosclerosis (FGS) (4 of 32, 13%, P = 0.04 by chi-square), but not in patients with membranous nephropathy (MGN) (1 of 19, 5%) or in patients with membranoproliferative glomerulonephritis (MPGN) (2 of 17, 12%). All of the patients with positive HCV serology had histories of intravenous (IV) drug use. Thus, HCV serology was negative in all of the patients with native glomerulopathies without histories of IV drug use. Compared with a group of 105 transplant patients without TxGN (1.8% HCV+), the prevalence of HCV antibodies was significantly higher in patients with acute (A)TxGN (12 or 41: 29%. P = 0.0004) and in patients with chronic (C)TxGN (9 of 27: 33%. P = 0.0004). Compared with controls, patients with ATxGN also had a significantly higher prevalence of serum immunoglobulin (Ig) M antibodies to cytomegalovirus (CMV) (3% and 26% of patients, respectively, P = 0.0004). However, there were no statistical associations between HCV and CMV serologies. These results do not support the postulate that HCV infection is associated with idiopathic native glomerulopathies; instead, the data suggest that the presence of HCV positivity in these patients can be explained by the inclusion of patients with a history of IV drug use. In contrast, these studies demonstrate for the first time an association between HCV infection and transplant glomerulopathies.

Case-Control Studies↗
PubMed1996

Loin pain-hematuria syndrome associated with thin glomerular basement membrane disease and hemorrhage into renal tubules.

Loin pain-hematuria (LPH) syndrome is a poorly understood disorder in which the patients, mainly young women, experience unexplained severe chronic unilateral or bilateral flank pain associated with gross and/or microscopic hematuria. By contrast, thin glomerular basement membrane (GBM) disease is generally thought to be a benign disorder, affecting males and females equally, in which the major manifestation is asymptomatic microscopic hematuria. Herein we describe seven patients (6 females, 1 male) in whom thin GBM appeared to be the cause of the LPH syndrome. The gross hematuria in these patients could be attributed to thin GBM disease because the renal biopsy demonstrated red cells in renal tubules (indicating glomerular hematuria) and the only glomerular abnormality present with thin GBM. In addition, the other causes of gross hematuria were excluded by appropriate testing. The flank pain in these patients might also have been the result of their thin GBM disease. This is suggested by renal biopsy findings of multiple renal tubules filled with red cells, apparently occluding the tubules. We suggest that occlusion of a relatively small fraction of renal tubules could cause renal pain if back-leak of glomerular filtrate occurred that was of sufficient magnitude to expand renal parenchymal volume and stretch the renal capsule. Preliminary observations suggest that treatment with the angiotensin converting enzyme (ACE) inhibitor enalapril importantly reduces the frequency and severity of the episodes of gross hematuria and flank pain in most patients. ACE inhibition might decrease glomerular hemorrhage in patients with think GBM by decreasing glomerular hydrostatic pressure. We conclude that (1) Thin GBM disease can be the cause of gross hematuria, apparently as a result of rupture of thin GBM. (2) Rupture of thin GBM resulting in hemorrhage into renal tubules may be the cause of the flank pain and gross hematuria in some patients with the LPH syndrome.

Adult↗
PubMed1995

Patterns of inflammatory vascular endothelial changes in murine liver grafts.

We have investigated the vascular endothelial phenotypes found at various times posttransplant in murine B10-->C3H liver grafts. In this model, liver allografts are spontaneously accepted, and survive indefinitely unless the recipient is first allosensitized with a skin allograft, in which case the liver allografts are rejected within five days. In our previous studies, allograft inflammation was associated with the development of vascular endothelial reactivity with the mAbs MECA-32 and M/K-2 (anti-VCAM-1). We observed that vascular endothelia in both liver isografts and allografts develop reactivity with MECA-32 mAb within two days of transplantation, indicating endothelial activation in both situations. In contrast, only the endothelia in liver allografts develop VCAM-1 expression, as detected with M/K-2 mAb. VCAM-1 was expressed in both rejecting and accepting liver allografts, demonstrating that endothelial VCAM-1 expression is indicative of ongoing graft inflammation but not necessarily graft rejection. Liver parenchymal cells did not appear to develop reactivity with either antibody under any of the conditions tested. In contrast, bile duct epithelia developed M/K-2 reactivity (VCAM-1 expression), but not MECA-32 reactivity in liver allografts, but not isografts. These data demonstrate alloantigen-dependent and alloantigen-independent patterns of endothelial behavior in murine liver grafts that are quite similar to those found in murine cardiac grafts. Further, they demonstrate that the expression of VCAM-1 by graft endothelia is not diagnostic for acute rejection of liver allografts.

Animals↗
PubMed1995

The role of interferon beta in human cytomegalovirus-mediated inhibition of HLA DR induction on endothelial cells.

Human cytomegalovirus (HCMV), a member of the virus family Herpesviridae that is associated with extensive worldwide morbidity and mortality in immunocompromised hosts, inhibits interferon-gamma (IFN gamma)-mediated induction of human leukocyte antigen (HLA) class II antigens on endothelial cells. In this study, the ability of HCMV-infected endothelial cells to synthesize interferon-beta (IFN beta), and the role of IFN beta in HCMV-mediated inhibition of HLA class II induction, was investigated. As determined by an encephalomyocarditis virus protection assay, HCMV-infected endothelial cell culture supernatants contained 240 IU/ml of IFN type I activity, of which 99.9% was IFN beta, as compared to the absence of IFN beta in mock-infected culture supernatants. UV-irradiated supernatants from HCMV-infected cultures inhibited induction of HLA class II in noninfected cultures by 24%. This inhibition could be abolished with 500 NU/ml of anti-IFN beta antibody. Addition of anti-IFN beta antibody directly to HCMV-infected cultures mitigated but did not abolish HLA class II antigen inhibition. Dual immunohistochemistry for HCMV and HLA DR demonstrated that infected cells, in contrast to noninfected cells, were rarely induced to express HLA class II even in the presence of anti-IFN beta antibody. These findings suggest that HCMV inhibits induction of HLA class II antigens by IFN beta dependent and independent mechanisms.

Cells, Cultured↗
PubMed1995

Cytomegalovirus infection is associated with absence of alveolar epithelial cell HLA class II antigen expression.

Cytomegalovirus (CMV) pneumonia is associated with the development of secondary immunosuppression with resultant bacterial and fungal superinfections. Because class II HLA expression within the lung may be important in normal pulmonary cell-mediated immunity, the association of CMV infection of alveolar epithelial cells (AEC) with an absence of HLA class II antigens was tested. Using dual-labeling immunohistochemistry to detect CMV, AEC, endothelial cells, macrophages, and HLA class II antigens, lung tissue from patients whom died with CMV pneumonia was examined. Seventy-five percent of infected cells were AEC. In contrast to adjacent noninfected AEC, which expressed HLA-DR antigens, 91% of infected AEC were negative. There was no difference in this expression pattern between patients with or without AIDS. The absence of HLA class II antigens on infected AEC may account, in part, for the secondary immunosuppression associated with CMV pneumonia.

AIDS-Related Opportunistic Infections↗
PubMed1995

Bidirectional transmission of infectious cytomegalovirus between monocytes and vascular endothelial cells: an in vitro model.

Cytomegalovirus (CMV) infects multiple tissues and organs; however, mechanisms of dissemination remain elusive. Although hematogenous spread has been implicated, in vitro studies have generally indicated that peripheral blood mononuclear cells (PBMC) do not support the complete viral reproductive cycle. Since CMV infects endothelial cells (EC), the hypothesis that PBMC can be productively infected by contact with CMV-infected EC was tested by coculturing PBMC with CMV-infected endothelial monolayers. Dual immunohistochemical staining for mononuclear cell markers and CMV-specific antigens demonstrated infection of up to 30% of monocytes adhering to EC. To determine if infected monocytes could transmit infectious virus, they were separated from EC, replated in culture wells, and then overlaid with fresh EC. The subsequent appearance of CMV-positive cytopathic foci within the overlaid monolayers indicated that these monocytes were capable of transmitting infectious virus. Thus, these results support an interactive role for the endothelium and circulating monocytes in the dissemination of this clinically problematic virus.

Biological Transport↗
PubMed1994

Divergent patterns of ELAM-1, ICAM-1, and VCAM-1 expression on cytomegalovirus-infected endothelial cells.

Endothelial cells, one of several in vivo host cells for cytomegalovirus (CMV), participate in solid organ allograft rejection in part through the expression of leukocyte adhesion molecules. The hypothesis that CMV infection alters the constitutive and induced expression of ELAM-1, ICAM-1, and VCAM-1 on infected human umbilical vein endothelial cells (HUVECs) was examined. HUVECs were infected with an endothelial cell-propagated strain of CMV (VHL/E) for various periods, treated with tumor necrosis factor-alpha (TNF alpha), and examined by flow cytometry or immunohistochemically dual-labeled with monoclonal antibodies to CMV immediate early nuclear protein and ELAM-1, ICAM-1, or VCAM-1. Neither ELAM-1 nor VCAM-1 was induced on CMV-infected HUVECs, and treatment with TNF alpha treatment did not result in their induction. In contrast, ICAM-1 was induced on infected HUVECs by 24 hr postinfection. Endothelial ICAM-1 induction may represent a mechanism by which CMV infection exacerbates the recipient cellular immune response to allografts.

Antibodies, Viral↗
PubMed1994

Alloantigenicity of human endothelial cells. III. Quantitated indirect presentation of endothelial alloantigens to human helper T lymphocytes.

We have investigated the contribution of monocytes (Mo) to the activation of purified human T cells by allogeneic human vascular endothelial cells (HUVEC). We have previously demonstrated that allogeneic HUVEC stimulate IL-2 production by CD8+ helper T lymphocytes (HTL), but not CD4+ HTL, in the absence of accessory Mo. We now show that addition of responder-autologous Mo to such cultures stimulates a high frequency of CD4+ HTL (1/6500), but no additional CD8+ HTL (1/35,000), as detected by limiting dilution analysis (LDA). The CD4+ HTL production of IL-2 increased with increasing numbers of Mo. Monoclonal antibodies to MHC class II interfered with HTL responses to allogeneic HUVEC in the presence, but not in the absence of autologous Mo. In contrast, IFN-gamma-treated HUVEC stimulated a high frequency of CD4+ HTL in the absence of autologous Mo. However, deletion experiments revealed that the population of HTL responsive to IFN-gamma-treated HUVEC is distinct from the population that responds to HUVEC in the presence of autologous Mo. These data suggest that Mo promote IL-2 production by presenting HUVEC-derived alloantigens via MHC class II molecules to CD4+ HTL, rather than by providing cytokines that promote more efficient IL-2 production by CD8+ HTL, or by inducing MHC class II expression on the HUVEC. In general, these data demonstrate that autologous Mo can play a significant role in the response of T cells to allogeneic HUVEC. Further, they demonstrate that the activation of human HTL by allogeneic HUVEC is complex, and can occur by at least three pathways: (1) direct stimulation of a small number of CD8+ HTL, but no CD4+ HTL, by quiescent HUVEC, (2) direct stimulation of a large number of CD4+ HTL by IFN-gamma-treated HUVEC, and (3) indirect stimulation of a different subset of CD4+ HTL by HUVEC in the presence of autologous monocytes. These three pathways of alloactivation are not unique to allogeneic HUVEC, but this experimental system provides a convenient and relevant model with which each pathway can be easily and independently investigated.

Antibodies, Monoclonal↗
PubMed1994

Alloantigenicity of human endothelial cells. IV. Derivation, characterization, and utilization of gonadal vein endothelia to control endothelial alloantigenicity during lymphocyte-endothelial interactions.

Most previous studies to evaluate endothelial cell-T lymphocyte interactions have used human peripheral blood as a source of T lymphocytes and human umbilical vein endothelial cells as a source of endothelia. Implicit in this experimental system are allogeneic lymphocyte-endothelial interactions, which are largely ignored. To overcome this problem, we isolated gonadal vein endothelial cells (GVEC) along with matched splenic macrophages and T lymphocytes from cadaveric donors, thus providing a completely autologous series of cells for experimentation. First, GVEC were analyzed for morphology, surface phenotype, and cytokine mRNA expression, and found to be indistinguishable from human umbilical vein endothelial cells. Using this system, we observed that irradiated GVEC were able to promote a 2- to 3-fold increase in the proliferation of matched autologous splenic T cells after PHA stimulation. This indicates that the costimulator activity of endothelial cells reported by others is an intrinsic property of endothelial cells, and is not a consequence of endothelial alloantigens. We also used this system to assess the relative abilities of GVEC and macrophages obtained from the same donor to stimulate the proliferation of purified allogeneic CD3+ PBL. We found the following hierarchy of alloantigenicity in this experimental system: splenic macrophages > IFN-gamma-treated GVEC >> untreated GVEC = TNF alpha-treated GVEC. These studies demonstrate that allogeneic macrophages are intrinsically more antigenic than endothelial cells derived from the same donor. Furthermore, they illustrate the utility of this experimental system to obtain data regarding lymphocyte-endothelial interactions that are otherwise unobtainable.

Base Sequence↗
PubMed1994

Xanthogranulomatous pyelonephritis in renal allografts: report of 2 cases.

We report 2 cases of xanthogranulomatous pyelonephritis that occurred in renal transplant recipients. Both cases were successfully treated with antibiotics. The traditional treatment of choice has been nephrectomy. No graft was lost as a result of xanthogranulomatous pyelonephritis and no nephrectomy was required in either patient. The course of these 2 patients is discussed and literature on this disease is reviewed.

Female↗
PubMed1994

Effect of recombinant erythropoietin therapy on autoimmunity in systemic lupus erythematosus.

Previous studies of the in vitro effects of recombinant erythropoietin (rEPO) on T and B cells and studies of lymphocyte subsets in dialysis patients receiving rEPO therapy suggest that rEPO might augment immune responses. In the present study indices of autoimmunity (antinuclear antibody, anti-double-stranded DNA, and antiphospholipid antibody [immunoglobulins G and M]) were measured before, during, and after rEPO therapy in five systemic lupus erythematosus patients without renal failure (mean serum creatinine, 1.5 +/- 0.3 mg/dL). The rEPO therapy was self-administered by subcutaneous injection in doses ranging from 4,000 units once weekly to 3,000 units three times weekly for 3 to 7 months. On rEPO therapy, each patient experienced an increase in hematocrit. The mean baseline hematocrit increased from 32 +/- 2.0 to a peak of 42.2 +/- 3 (P < 0.001) at 3 to 7 months and then decreased to baseline values 1 to 2 months after rEPO was discontinued. During this time the indices of autoimmunity were not significantly changed by rEPO therapy. Systemic lupus erythematosus activity, assessed by serum C3, serum creatinine, urinalysis, and 24-hour proteinuria, also was unchanged by rEPO therapy. The rEPO therapy was generally well tolerated. However, one patient, who was also receiving replacement estrogen therapy and had high-titer antiphospholipid antibody, experienced episodes of thrombophlebitis while on rEPO therapy. In conclusion, we found no evidence that rEPO increases autoimmunity in systemic lupus erythematosus. However, we observed a temporal relationship between episodes of thrombophlebitis and rEPO therapy in a single patient with high-titer anticardiolipin antibody who was also receiving replacement estrogen therapy. These associations require further investigation.

Adult↗
PubMed1994

Association of thin glomerular basement membrane with other glomerulopathies.

In the present study we assessed the prevalence of thin glomerular basement membrane (TGBM) in a large group of native kidney biopsies done for evaluation of renal disease. TGBM was present in 54 of 1078 biopsies (5%). In 12 of 54 biopsies (24%), TGBM was the only abnormality present. In the remaining biopsies TGBM was associated with other pathologic diagnoses. The overall prevalence of TGBM in this series is comparable to previous population studies. TGBM is significantly more common in patients with IgA nephropathy and mesangial proliferative glomerulonephritis. Compared to control patients, individuals with TGBM were more likely to have a history of familial hematuria (14% vs. 43%, P = 0.02). Furthermore, examination of urinary sediments in first degree relatives of patients with TGBM demonstrated microscopic hematuria in 92% of families and, in those families, hematuria was present in 47 +/- 6% of relatives. In contrast, hematuria was discovered in 38% of families of control patients, affecting 25 +/- 5% of relatives. In conclusion, the presence of TGBM in a kidney biopsy is highly predictable for the presence of familial microscopic hematuria, even in patients in whom TGBM is associated with another glomerulopathy. The present data also indicate that patients with TGBM nephropathy often have concomitant IgA nephropathy and mesangial proliferative glomerulonephritis.

Basement Membrane↗
PubMed1994

Antibody depletion prolongs xenograft survival.

BACKGROUND: The lack of human organ donors has prompted a renewed interest in xenotransplantation. Xenoantibody is believed to be an initiator of a complex cascade of events ultimately ending in rapid xenograft destruction. METHODS: Cell-free plasma was obtained via plasmapheresis of the recipient canine. This plasma was then perfused in an ex vivo fashion through either the donor (pig) spleen or liver, allowing for specific antidonor antibody deposition in the "screening" organ, and is then returned to the animal. A porcine kidney is then transplanted to the dog, and the outcome is observed. RESULTS: We have used specific antibody depletion to prolong xenotransplant survival. In the untreated pig-to-dog combination, the transplanted pig kidney is destroyed by the dog in 13 minutes (mean). Adsorption using either the donor spleen or liver resulted in an increase of 3.4 hours and 7.8 hours of graft survival, respectively. The histologic picture of rejected kidneys after adsorption shows a modified form of rejection. CONCLUSIONS: In this pig-to-dog xenograft combination, xenoantibody adsorption allows for prolonged graft survival as compared with control animals. Subsequent xenograft destruction occurs but in a modified manner.

Adsorption↗
PubMed1994

Cytomegalovirus inhibits major histocompatibility class II expression on infected endothelial cells.

Persistent human cytomegalovirus (HCMV) infections are responsible for significant morbidity and mortality in immunocompromised individuals. One mechanism by which HCMV may develop persistence after primary infection is through inhibition of host cell human leukocyte antigen (HLA) class II expression with resultant escape from normal antiviral immune surveillance. Immunofluorescence flow cytometry of human endothelial cell (EC) cultures infected with HCMV AD169 and an EC propagated strain, VHL/E, showed a marked reduction in interferon-gamma (IFN-gamma)-induced surface expression of HLA-DR. This inhibition did not occur when EC were treated with ultraviolet-inactivated virus and IFN-gamma. HCMV, as determined by dual-labeling immunohistochemistry, inhibited induction of surface and cytoplasmic class II antigens specifically in infected cells. HCMV infection also inhibited IFN-gamma and tumor necrosis factor-alpha up-regulation of HLA class I expression. Northern blot analysis of infected, IFN-gamma-treated human umbilical vein endothelial cells revealed an absence of class II mRNA. Persistence of HCMV may result in part from its ability to inhibit HLA class II induction in infected cells.

Blotting, Northern↗
PubMed1993

Cellular localization of CD4 in the human placenta. Implications for maternal-to-fetal transmission of HIV.

CD4 is a 55-kDa glycoprotein that serves as an important cellular differentiation Ag and cell signaling protein on T lymphocytes, as well as a principal receptor for HIV-1 on a variety of cell types including lymphocytes. CD4 receptor expression in syncytiotrophoblasts, the principal cellular barrier in the human placenta, has not been clearly defined. Knowledge concerning the expression of the CD4 receptor on placental trophoblasts is important to define potential mechanisms of transmission of the virus between maternal blood and fetal tissues. Both mature and immature placenta (n = 10) were examined using an avidin D-based immunohistochemical procedure that permits clear morphologic distinction of cell types in placental sections. Syncytiotrophoblasts were defined using anti-cytokeratin mAb (AE1/3), whereas endothelial cells in placental villi were distinctly identified using a mAb directed to CD31. Placental Hofbauer cells (macrophages) and other leukocytes were identified by mAb staining of leukocyte common Ag (CD45). CD4 expression (identified by staining with three separate anti-CD4 mAb) was exclusively localized using this immunohistochemical method to leukocytes in placental villi (e.g., Hofbauer cells); however, no CD4 staining was evident in syncytiotrophoblasts, cytotrophoblasts, or villus endothelial cells. Furthermore, immunoaffinity-purified trophoblasts were negative for CD4 receptor expression. CD4 RNA was not identified in purified trophoblasts using both Northern blot assay and a sensitive polymerase chain reaction method to identify CD4 RNA. In addition, time course studies of purified trophoblasts immediately after purification and at 24, 48, and 72 h in culture indicated that CD4 RNA was not present as a transient, but labile transcript in trophoblasts. These data indicate that the transmission of HIV-1 across syncytiotrophoblasts may occur by mechanisms other than by binding the CD4 receptor and that tissue leukocytes (in particular Hofbauer cells) are likely the principal CD4+ cellular target of HIV-1 in the placenta.

Base Sequence↗
PubMed1993

Analysis of inflammatory endothelial changes, including VCAM-1 expression, in murine cardiac grafts.

We have employed a murine model of cardiac transplantation and two monoclonal antibodies, M/K-2 and MECA-32, to study the responses of graft endothelia during allograft rejection. Using immunohistologic techniques, we demonstrate that the monoclonal antibody M/K-2, which binds to the murine cellular adhesion molecule VCAM-1, reacts with an inducible endothelial epitope found in rejecting cardiac allografts, but not in cardiac isografts, normal cardiac tissues, or extracardiac vasculature from allografted mice. Similar, but focal, M/K-2 reactivity is also found in nontransplanted hearts undergoing virally induced myocarditis. M/K-2 reactivity does not develop in the nonrejecting cardiac allografts from nu/nu mice, and M/K-2 reactivity is found only in grafts that develop CD25+ graft-infiltrating cells--i.e., allografts but not isografts. PCR analyses of grafts during development of VCAM-1 expression indicate that allografts, but not isografts, contain mRNA for the cytokines IL-2 and IFN-gamma, and either of these cytokines may be associated with the expression of M/K-2 reactivity in rejecting allografts. Unlike M/K-2, MECA-32 identifies an inducible epitope that is observed on myocardial endothelia of both isografts and allografts, but not normal cardiac tissues. Further, expression of the MECA-32 epitope can occur in grafts that do not develop CD25+ infiltrating lymphocytes, since it is observed in isografts and the native hearts of transplanted or sham-operated mice. Indeed, MECA-32 reactivity may be T cell independent, since it is also found in nonrejecting allografts of nu/nu mice. PCR analyses of grafts during development of MECA-32 reactivity indicate that cardiac isografts contain mRNA for IL-1, IL-6, TNF, and lymphotoxin. One or more of these might be associated with induction of MECA-32 reactivity.

Animals↗
PubMed1993

In vitro induction of endothelial HLA class II antigen expression by cytomegalovirus-activated CD4+ T cells.

CMV has been associated with allograft rejection and transplantation-associated arteriosclerosis. CMV infects endothelium, the interface between allograft tissue and the host immune system. Although endothelial HLA class II expression is a hallmark of vascular rejection, CMV does not directly induce these antigens on infected endothelial cells (EC) and, indeed, renders them refractory to HLA DR induction by IFN-gamma. Our earlier studies have demonstrated, however, that CMV-infected EC are capable of eliciting vigorous activation responses by allogeneic, CMV-seropositive donor-derived CD4+ T cells. We now show that T cells thus activated can induce HLA DR expression on noninfected EC. Human umbilical vein endothelial cells (HUVEC) were inoculated at low titer with CMV strain VHL/E, cocultured with allogeneic, CMV-seropositive or CMV-seronegative donor-derived CD4+ T cells, then dual immunohistochemically stained for CMV antigen and HLA DR, or assayed for HLA DR expression by fluorescence flow cytometry. Results demonstrated that HLA DR was induced in 20-70% of HUVEC in monolayers containing less than 0.5% CMV-infected EC after coculture with CMV-seropositive donor-derived T cells. No such induction was observed in experiments employing T cells isolated from CMV-seronegative individuals. Expression of this antigen was strictly limited to noninfected cells. Rare HLA DR induction was observed in virus-free cocultures. To determine whether endothelial HLA DR was induced by a soluble factor(s) elaborated by activated T cells, noninfected HUVEC monolayers were treated for 72 hr with cell-free supernatant from CMV-infected or noninfected HUVEC/T cell cocultures and assayed as above. Again, HLA DR expression was induced by supernatant from CMV-positive cocultures (only when cocultured T cells were isolated from CMV-seropositive donors), but not by supernatant from CMV-negative cocultures or from T cells cultured alone. The soluble factor was identified as IFN-gamma by the complete attenuation of HLA DR induction by anti-IFN-gamma mAb. These findings suggest that allograft endothelium harboring low level CMV may be capable of eliciting host CD4+ T cell activation, and that consequent release of IFN-gamma is capable of inducing endothelial HLA class II expression, as observed in vascular rejection and transplantation-associated arteriosclerosis. Results of these studies thus provide insight into mechanisms that may help elucidate the association between CMV and rejection-related immune events in the allograft.

Antibodies, Monoclonal↗