Implication of gammadelta T cells in the human immune response to cytomegalovirus.
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In normal individuals, gammadelta T cells account for less than 6% of total peripheral T lymphocytes and mainly express T-cell receptor (TCR) Vdelta2-Vgamma9 chains. We have previously observed a dramatic expansion of gammadelta T cells in the peripheral blood of renal allograft recipients only when they developed cytomegalovirus (CMV) infection. This increase was long lasting (more than 1 year), was associated with an activation of gammadelta T cells, and concerned only Vdelta1 or Vdelta3 T-cell subpopulations. Analysis of gammadelta TCR junctional diversity revealed that CMV infection in these patients was accompanied by (a) a marked restriction of CDR3 size distribution in Vdelta3 and, to a lesser extent, in Vdelta1 chains; and (b) a selective expansion of Vdelta1 cells bearing recurrent junctional amino acid motifs. These features are highly suggestive of an in vivo antigen-driven selection of gammadelta T-cell subsets during the course of CMV infection. Furthermore, Vdelta1 and Vdelta3 T cells from CMV-infected kidney recipients were able to proliferate in vitro in the presence of free CMV or CMV-infected fibroblast lysates but not uninfected or other herpes virus-infected fibroblast lysates. This in vitro expansion was inhibited by anti-gammadelta TCR mAb's. These findings suggest that a population of gammadelta T cells might play an important role in the immune response of immunosuppressed patients to CMV infection. (+info)
Low incidence of transplant coronary artery disease in Chinese heart recipients.
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OBJECTIVES: This study sought to assess the incidence of transplant coronary artery disease (CAD) in Chinese heart recipients. BACKGROUND: The prevalence of transplant CAD detected by angiography at 1, 2 and 4 years after heart transplantation was 11%, 22% and 45%, respectively. The incidence of transplant CAD in Chinese heart recipients has not been reported. METHODS: For those recipients surviving for more than 1 year after transplantation, coronary angiography was performed annually for surveillance of transplant CAD. The recipient characteristics, donor characteristics, rejection episodes, medication and human leukocyte antigen (HLA) mismatches were recorded. RESULTS: Fifty patients were included in this study. Thirteen (26%) recipients had ischemic heart disease. Two patients (4%) had active cytomegalovirus (CMV) infection after transplantation. The mean number of rejection episodes in the 1st year after transplantation was 1.15. Among 47 patients with complete data of donor and recipient histocompatibility antigens, there were seven patients (14.9%) with two or fewer HLA mismatches. Among 74 angiograms of 50 patients reviewed, only one patient had discrete stenosis less than 50% in the middle portion of the left anterior descending artery at 1 year after transplantation. The cumulative incidence of transplant CAD was 2% at 1 year and 2% at 2 and 4 years after transplantation. CONCLUSIONS: The incidence of transplant CAD was low in Chinese heart transplant recipients. Low percentage of ischemic heart disease in recipients, low occurrence of active CMV infection and rejection episodes after transplantation, less racial disparity, and lower HLA mismatches may be the important factors. (+info)
Immunologic parameters as predictive factors of cytomegalovirus disease in renal allograft recipients.
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Cytomegalovirus (CMV) disease is a major problem in renal transplant recipients, but few predictive markers of the disease are known. Several immunologic parameters of potential relevance for the defense against CMV were measured after renal transplantation in 25 patients before any manifestations of CMV infection occurred. In 10 patients who later developed CMV disease, plasma levels of interleukin-8 were significantly higher, whereas the levels of macrophage inflammatory protein-1alpha (MIP-1alpha) were significantly lower than in 15 patients who did not develop CMV disease. Also, lower numbers of CD4+ and CD8+ lymphocytes were observed in patients who later had CMV disease. These findings were independent of previous rejection therapy and were particularly pronounced in patients with primary CMV infection. Interleukin-8 and MIP-1alpha may be predictive markers of CMV disease and could be of potential use in selecting patients for prophylactic treatment. (+info)
Cutting edge: a novel viral TNF receptor superfamily member in virulent strains of human cytomegalovirus.
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The UL144 open reading frame found in clinical isolates of human CMV (HCMV) encodes a structural homologue of the herpesvirus entry mediator, a member of the TNFR superfamily. UL144 is a type I transmembrane glycoprotein that is expressed early after infection of fibroblasts; however, it is retained intracellularly. A YXXZ motif in the highly conserved cytoplasmic tail contributes to UL144 subcellular distribution. The finding that no known ligand of the TNF family binds UL144 suggests that its mechanism of action is distinct from other known viral immune evasion genes. Specific Abs to UL144 can be detected in the serum of a subset of HCMV seropositive individuals infected with HIV. This work establishes a novel molecular link between the TNF superfamily and herpesvirus that may contribute to the ability of HCMV to escape immune clearance. (+info)
Human virus-specific CD8+ CTL clones revert from CD45ROhigh to CD45RAhigh in vivo: CD45RAhighCD8+ T cells comprise both naive and memory cells.
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It has been generally believed that human CD8+ memory cells are principally found within the CD45ROhigh population. There are high frequencies of CD8+ memory CTL specific for the human CMV tegument phosphoprotein pp65 in PBMC of long-term virus carriers; the large population of memory CTL specific for a given pp65 peptide contains individual CTL clones that have greatly expanded. In this study, we found high frequencies of pp65 peptide-specific memory CTL precursors in the CD45ROhighCD45RA- population, but also appreciable frequencies in the CD45RAhigh subpopulation. Because the majority of CD8+ T cells in PBMC are CD45RAhigh, more of the total pp65-specific memory CTL pool is within the CD45RAhigh than in the CD45ROhigh compartment. Using clonotypic oligonucleotide probes to quantify the size of individual pp65-specific CTL clones in vivo, we found the CD45RAhigh population contributed 6- to 10-fold more than the CD45ROhigh population to the total virus-specific clone size in CD8+ cells. During primary CMV infection, an individual virus-specific CTL clone was initially CD45ROhigh, but after resolution of infection this clone was detected in both the CD45ROhigh and the CD45RAhigh populations. We conclude that CD45RA+ human CD8+ T cells do not solely comprise naive cells, but contain a very significant proportion of memory cells, which can revert from the CD45ROhigh to CD45RAhigh phenotype in vivo. (+info)
Role of retinal vascular endothelial cells in development of CMV retinitis.
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PURPOSE: Although cytomegalovirus (CMV) retinitis is known to occur in association with retinal microangiopathy in individuals with marked immunodeficiency, glial cells are believed to be the initial target cells in the development of retinitis. Moreover, it has been hypothesized that CMV gains access to the retinal glia because of altered vascular permeability. In an attempt to address the hypothesis, we studied 30 autopsy eyes of AIDS patients with systemic CMV infection, with or without clinically apparent CMV retinitis. METHODS: The autopsy eyes were processed in three ways. First, dual immunohistochemical studies were done by using anti-CMV antibodies for immediate early, early, and late antigens. The retinal cell types infected with the virus were then determined by using anti-GFAP, anti-VonWillebrand's factor, neuronal specific enolase, and leukocyte marker CD68. Second, selected eyes were processed for in situ hybridization with DNA probe specific to CMV. Third, an eye with clinically apparent CMV retinitis was submitted for electron microscopic examination. RESULTS: At the site of retinal necrosis in those eyes with a clinical diagnosis of CMV retinitis, the immunohistochemical, in situ hybridization, and ultrastructural examinations revealed that CMV was present primarily in the Muller cells and in perivascular glial cells. Adjacent to these infected cells, focal areas of positive staining for CMV antigen were seen in the glial cells, neuronal cells, and retinal pigment epithelial cells. At these sites most of the retinal capillaries were devoid of endothelial cells. Few vessels located at the advancing margin of retinal necrosis showed the presence of viral proteins in the endothelial cells. CONCLUSIONS: The present results indicate that retinal vascular endothelial cells could be the initial target in the development of viral retinitis, with subsequent spread of the infection to perivascular glia, Muller cells, and other retinal cells, including the retinal pigment epithelium. (+info)
Cytomegalovirus pneumonia in a patient with breast cancer on chemotherapy: case report and review of the literature.
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Cytomegalovirus (CMV) pneumonia in the setting of non-transplantation patients is a rarity. We present a case of CMV pneumonitis in a woman with stage IV breast cancer, with brain metastases, receiving both chemotherapy and systemic corticosteroids. A review of the literature reveals this as a unique case. Potential viral etiologies should therefore be considered in cancer patients with pneumonia receiving non-transplantation chemotherapy-regimens, particularly if steroids are a component of their therapy. (+info)
Concurrent Pneumocystis carinii and cytomegalovirus pneumonia after autologous peripheral blood stem cell transplantation.
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A 46-year-old woman developed concurrent CMV and Pneumocystis carinii pneumonia (PCP) 140 days after autologous peripheral blood stem cell transplantation (APBSCT) for AML. She was seropositive for CMV before undergoing APBSCT and had required prednisone for immune thrombocytopenia and allergic dermatitis for 9 weeks prior to the onset of pneumonia. She had also been receiving PCP prophylaxis with pentamidine aerosol every month for 3 months before developing symptoms. The pneumonia was complicated by severe hypoxia, requiring ventilator support and pneumothorax requiring chest tube thoracostomy. She recovered following treatment with trimethoprim-sulfamethoxazole (TMP-SMX), prednisone, gancyclovir and intravenous immunoglobulin. Although the overall incidence of severe CMV disease is low after APBSCT, preventive measures such as surveillance culture and secondary prophylaxis with gancyclovir may be warranted in patients whose cellular immune response is further compromised by corticosteroid use or other factors. (+info)