Cytomegalovirus (CMV) infection is associated with allograft rejection but the mechanisms behind are poorly defined yet. Although cross-reactivity of T cells to alloantigen and CMV has been hypothesized, direct evidence in patients is lacking. In this observational cohort study, we tested the pre-transplant effector/memory T cell response to CMV peptide pools and alloantigen in 78 living donor/recipient pairs using the interferon-gamma Enzyme-Linked ImmunoSpot (ELISPOT) assay. To prove the hypothesis of cross-reactivity, we analyzed by applying next-generation sequencing the T cell receptor ß (TCR- ß) repertoire of CMV- and alloantigen-reactive T cells enriched from peripheral pre-transplant blood of 11 CMV-seropositive and HLA class I mismatched patients. Moreover, the TCR-repertoire was also analyzed in the allograft biopsies of those patients. There was a significant association between the presence of pre-transplant CMV immediate-early protein 1 (IE-1)-specific effector/memory T cells and acute renal allograft rejection and function (p = 0.01). Most importantly, we revealed shared TCR-ß sequences between CMV-IE1 and donor alloantigen-reactive T cells in all pre-transplant peripheral blood samples analyzed in CMV-seropositive patients who received HLA class I mismatched grafts. Identical TCR sequences were also found in particular in post-transplant allograft biopsies of patients with concomitant CMV infection and rejection. Our data show the presence of functional, cross-reactive T cells and their clonotypes in peripheral blood and in kidney allograft tissue. It is therefore likely that CMV-donor cross-reactivity as well as CMV specific T cell elicited inflammation is involved in the processes that affect allograft outcomes.
- MeSH
- alografty MeSH
- biopsie MeSH
- cytomegalovirové infekce * etiologie genetika imunologie patologie MeSH
- Cytomegalovirus imunologie MeSH
- dospělí MeSH
- imunologická paměť * MeSH
- isoantigeny genetika imunologie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- receptory antigenů T-buněk alfa-beta * imunologie MeSH
- T-lymfocyty * mikrobiologie patologie MeSH
- transplantace ledvin * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
CD58 is an adhesion molecule that is known to play a critical role in costimulation of effector cells and is intrinsic to immune synapse structure. Herein, we describe a virally encoded gene that inhibits CD58 surface expression. Human cytomegalovirus (HCMV) UL148 was necessary and sufficient to promote intracellular retention of CD58 during HCMV infection. Blocking studies with antagonistic anti-CD58 mAb and an HCMV UL148 deletion mutant (HCMV∆UL148) with restored CD58 expression demonstrated that the CD2/CD58 axis was essential for the recognition of HCMV-infected targets by CD8+ HCMV-specific cytotoxic T lymphocytes (CTLs). Further, challenge of peripheral blood mononuclear cells ex vivo with HCMV∆UL148 increased both CTL and natural killer (NK) cell degranulation against HCMV-infected cells, including NK-driven antibody-dependent cellular cytotoxicity, showing that UL148 is a modulator of the function of multiple effector cell subsets. Our data stress the effect of HCMV immune evasion functions on shaping the immune response, highlighting the capacity for their potential use in modulating immunity during the development of anti-HCMV vaccines and HCMV-based vaccine vectors.
- MeSH
- buněčná imunita * MeSH
- buňky NK imunologie patologie MeSH
- CD8-pozitivní T-lymfocyty imunologie patologie MeSH
- cytomegalovirové infekce genetika imunologie patologie MeSH
- Cytomegalovirus genetika imunologie MeSH
- imunitní únik * MeSH
- lidé MeSH
- proteiny virové fúze genetika imunologie MeSH
- transformované buněčné linie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Pacienti po transplantaci ledviny jsou v riziku různých infekčních komplikací a více než polovina z nich se v časném potransplantačním období s nějakou infekční komplikací setká. Přesto, že se z dlouhodobého pohledu riziko závažných infekčních komplikací v časném pooperačním období snížilo, zůstávají infekce v prvních 6 měsících nejčastější příčinou morbidity. V pozdějším období se objevují infekce, které postihují štěp ledviny a některé z nich se vyskytují pouze u pacientů v imunosupresi. Mezi klinicky nejvýznamnější a nejčastější nejvýznamnější patří polyomavirová nefropatie. Klíčová slova: polyomavirová nefropatie – transplantace ledviny – infekční komplikace
Immunosuppressed kidney transplant recipients are at risk for a variety of infectious complications and more than half of them suffered from this complication in the early post-transplant period. Despite the fact that the long term risk of serious infectious complications in the early postoperative period decreased, remain the infection the most frequent cause of morbidity in the first 6 months after transplant. It is important to realize that the clinical manifestations of infection in the compromised host are variable and often atypical. In the later period, infections that affect the kidney graft become clinically important, and some of them occur only in immunosuppressed patients. Here we will discuss polyomavirus nephropathy which represents the most important and most frequent viral disease of renal allografts. Keywords: polyomavirus nephropathy – kidney transplantation – infectious complications
- Klíčová slova
- polyomavirová nefropatie, infekční komplikace,
- MeSH
- biopsie MeSH
- cytomegalovirové infekce patologie MeSH
- imunosupresivní léčba škodlivé účinky MeSH
- infekce virem Epsteina-Barrové patologie MeSH
- intersticiální nefritida * diagnóza etiologie patologie MeSH
- lidé MeSH
- polyomavirové infekce * diagnóza patologie MeSH
- pooperační komplikace MeSH
- pyelonefritida patologie MeSH
- transplantace ledvin * MeSH
- virus BK izolace a purifikace patogenita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Common variable immunodeficiency (CVID) is the most frequent clinically relevant primary immunodeficiency and shows enormous heterogeneity in clinical presentation. Despite clinical immunodeficiency, opportunistic infections are not a typical manifestation of CVID. A retrospective study of 32 patients followed up for 335 patient-years was performed to determine the frequency of cytomegalovirus (CMV) disease. Symptomatic CMV infection was documented in 3 CVID patients. Patients No. 1 and 2 suffered from CMV pneumonia, with complications due to atypical mycobacteriosis in patient No. 1. Patient No. 3 suffered from CMV enteritis. A history of cancer and chronic hepatitis C infection (patient No. 1), immunosuppressive therapy for interstitial lung disease (patient No. 2) and serious enteropathy complicated with malnutrition (patient No. 3) may have contributed to the complications despite only mild abnormalities in T-cell subpopulations. The direct detection of CMV in bronchoalveolar lavage, stool or tissue samples was the most beneficial diagnostic laboratory method, whereas the detection of CMV DNA in blood did not produce positive results. Adequate treatment of CMV disease led to significant clinical improvement in all 3 patients. The frequency of CMV disease appears to be higher than previously described. In our experience, the probability of opportunistic infections in CVID patients increases with secondary comorbidities and their management.
- MeSH
- atypické mykobakteriální infekce komplikace diagnóza patologie virologie MeSH
- běžná variabilní imunodeficience komplikace diagnóza patologie virologie MeSH
- bronchoalveolární lavážní tekutina virologie MeSH
- cytomegalovirové infekce komplikace diagnóza patologie virologie MeSH
- Cytomegalovirus MeSH
- DNA virů izolace a purifikace MeSH
- enteritida komplikace diagnóza patologie virologie MeSH
- feces virologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- virová pneumonie komplikace diagnóza patologie virologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
The research objective was to study frequency of antenatal infection and record probable clinical manifestations in 100 children with HCMV born from mother with HCMV in blood and mononuclear cells. The study identified poly-systemic internal organ damage in neonates due to prenatal HCMV. Research procedures involved study of 100 pairs of patients, Mother-Child tandem, using regular clinical assessment methods per algorithm and HCMV diagnostic methods: ELISA, affinity and avidity of HCMV antibodies, and HCMV genome identification via PCR method in blood plasma and mononuclear cells. Initial clinical disease manifested in 71% of children during late neonatal period. Children who died of HCMV (5%) were infected antenatal, and 39% were born prematurely. Embryonic stigma found in five cases. HCMV’s affinity to different tissues during the process of embryogenesis leads of poly-systemic damage and results in various clinical manifestations in the postnatal period. HCMV’s ability to invade mononuclear blood cells jeopardizes the antivirus defense system. The research is vital to deter the transmission of the virus and provide HCMV specific treatment to couples planning to have children.
- MeSH
- antivirové látky aplikace a dávkování MeSH
- cytomegalovirové infekce farmakoterapie krev patologie MeSH
- herpes simplex farmakoterapie krev patologie MeSH
- herpes zoster farmakoterapie krev patologie MeSH
- hostitel s imunodeficiencí účinky léků MeSH
- lidé MeSH
- virová hepatitida u lidí farmakoterapie virologie MeSH
- virus Epsteinův-Barrové MeSH
- Check Tag
- lidé MeSH
- MeSH
- cytomegalovirové infekce diagnóza patologie prevence a kontrola MeSH
- dospělí MeSH
- ganciklovir terapeutické užití MeSH
- lidé MeSH
- pooperační komplikace diagnóza patologie terapie MeSH
- primární prevence MeSH
- transplantace srdce MeSH
- výběr pacientů MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- cytomegalovirové infekce diagnóza patologie MeSH
- dospělí MeSH
- lidé MeSH
- methylprednisolon terapeutické užití MeSH
- pitva MeSH
- pneumonie patologie virologie MeSH
- syndromy imunologické nedostatečnosti diagnóza komplikace krev MeSH
- trombocytopenie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
