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1.
Am J Transplant ; 16(3): 833-40, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26663441

RESUMO

The authors previously identified plasma plasminogen activator inhibitor-1 (PAI-1) level as a quantitative lung injury biomarker in primary graft dysfunction (PGD). They hypothesized that plasma levels of PAI-1 used as a quantitative trait could facilitate discovery of genetic loci important in PGD pathogenesis. A two-stage cohort study was performed. In stage 1, they tested associations of loci with PAI-1 plasma level using linear modeling. Genotyping was performed using the Illumina CVD Bead Chip v2. Loci meeting a p < 5 × 10(-4) cutoff were carried forward and tested in stage 2 for association with PGD. Two hundred ninety-seven enrollees were evaluated in stage 1. Six loci, associated with PAI-1, were carried forward to stage 2 and evaluated in 728 patients. rs3168046 (Toll interacting protein [TOLLIP]) was significantly associated with PGD (p = 0.006). The increased risk of PGD for carrying at least one copy of this variant was 11.7% (95% confidence interval 4.9-18.5%). The false-positive rate for individuals with this genotype who did not have PGD was 6.1%. Variants in the TOLLIP gene are associated with higher circulating PAI-1 plasma levels and validate for association with clinical PGD. A protein quantitative trait analysis for PGD risk prioritizes genetic variations in TOLLIP and supports a role for Toll-like receptors in PGD pathogenesis.


Assuntos
Biomarcadores/análise , Variação Genética/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Transplante de Pulmão/efeitos adversos , Disfunção Primária do Enxerto/diagnóstico , Locos de Características Quantitativas , Adulto , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Inibidor 1 de Ativador de Plasminogênio/sangue , Disfunção Primária do Enxerto/sangue , Disfunção Primária do Enxerto/etiologia , Prognóstico , Estudos Prospectivos
2.
Am J Transplant ; 11(11): 2517-22, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21883907

RESUMO

Primary graft dysfunction (PGD) after lung transplantation may result from ischemia reperfusion injury (IRI). The innate immune response to IRI may be mediated by Toll-like receptor and IL-1-induced long pentraxin-3 (PTX3) release. We hypothesized that elevated PTX3 levels were associated with PGD. We performed a nested case control study of lung transplant recipients with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) from the Lung Transplant Outcomes Group cohort. PTX3 levels were measured pretransplant, and 6 and 24 h postreperfusion. Cases were subjects with grade 3 PGD within 72 h of transplantation and controls were those without grade 3 PGD. Generalized estimating equations and multivariable logistic regression were used for analysis. We selected 40 PGD cases and 79 non-PGD controls. Plasma PTX3 level was associated with PGD in IPF but not COPD recipients (p for interaction < 0.03). Among patients with IPF, PTX3 levels at 6 and 24 h were associated with PGD (OR = 1.6, p = 0.02 at 6 h; OR = 1.4, p = 0.008 at 24 h). Elevated PTX3 levels were associated with the development of PGD after lung transplantation in IPF patients. Future studies evaluating the role of innate immune activation in IPF and PGD are warranted.


Assuntos
Proteína C-Reativa/metabolismo , Fibrose Pulmonar Idiopática/cirurgia , Transplante de Pulmão/fisiologia , Disfunção Primária do Enxerto/etiologia , Traumatismo por Reperfusão/complicações , Componente Amiloide P Sérico/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Fibrose Pulmonar Idiopática/fisiopatologia , Imunidade Inata , Transplante de Pulmão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/sangue , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/cirurgia , Traumatismo por Reperfusão/imunologia
3.
Am J Transplant ; 11(3): 561-7, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21299834

RESUMO

Primary graft dysfunction (PGD) is the leading cause of early posttransplant morbidity and mortality after lung transplantation. Clara cell secretory protein (CC16) is produced by the nonciliated lung epithelium and may serve as a plasma marker of epithelial cell injury. We hypothesized that elevated levels of CC16 would be associated with increased odds of PGD. We performed a prospective cohort study of 104 lung transplant recipients. Median plasma CC16 levels were determined at three time points: pretransplant and 6 and 24 h posttransplant. The primary outcome was the development of grade 3 PGD within the first 72 h after transplantation. Multivariable logistic regression was performed to evaluate for confounding by donor and recipient demographics and surgical characteristics. Twenty-nine patients (28%) developed grade 3 PGD within the first 72 h. The median CC16 level 6 h after transplant was significantly higher in patients with PGD [13.8 ng/mL (IQR 7.9, 30.4 ng/mL)] than in patients without PGD [8.2 ng/mL (IQR 4.5, 19.1 ng/mL)], p = 0.02. Elevated CC16 levels were associated with increased odds of PGD after lung transplantation. Damage to airway epithelium or altered alveolar permeability as a result of lung ischemia and reperfusion may explain this association.


Assuntos
Biomarcadores/sangue , Transplante de Pulmão/efeitos adversos , Disfunção Primária do Enxerto/sangue , Disfunção Primária do Enxerto/diagnóstico , Uteroglobina/sangue , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
4.
Am J Transplant ; 9(12): 2697-706, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20021479

RESUMO

Obliterative bronchiolitis (OB) limits the long-term success of lung transplantation, while T-cell effector mechanisms in this process remain incompletely understood. Using the murine heterotopic tracheal transplant model of obliterative airway disease (OAD) to characterize airway allograft rejection, we previously reported an important role for CD8(+) T cells in OAD. Herein, we studied the role of CD154/CD40 costimulation in the regulation of allospecific CD8(+) T cells, as airway rejection has been reported to be CD154-dependent. Airway allografts from CD154(-/-) recipients had significantly lower day 28 OAD scores compared to wild-type (WT) recipients, and adoptive transfer of CD8(+) T cells from WT recipients, but not CD154(-/-) recipients, were capable of airway rejection in fresh CD154(-/-) allograft recipients. Intragraft CD8(+) T cells from CD154(-/-) mice showed similar expression of the surface markers CD69, CD62L(low) CD44(high) and PD-1, but markedly impaired IFN-gamma and TNF-alpha secretion and granzyme B expression versus WT controls. Unexpectedly, intragraft and systemic CD8(+) T cells from CD154(-/-) recipients demonstrated robust in vivo expansion similar to WT recipients, consistent with an uncoupling of proliferation from effector function. Together, these data suggest that a lack of CD154/CD40 costimulation results in ineffective allospecific priming of CD8(+) T cells required for murine OAD.


Assuntos
Bronquiolite Obliterante/imunologia , Ligante de CD40/deficiência , Linfócitos T CD8-Positivos/imunologia , Transferência Adotiva , Animais , Bronquiolite Obliterante/prevenção & controle , Proliferação de Células , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Traqueia/transplante
5.
Indian J Med Microbiol ; 22(2): 133, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-17642715
7.
Cell Immunol ; 118(2): 394-405, 1989 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2521309

RESUMO

Accessory cells are required for proliferation and antibody synthesis of B lymphocytes and proliferation of T lymphocytes in primary immune responses in vitro. The obligatory cells derived from the spleen are referred to as dendritic cells. Accessory cells were isolated from normal adult livers which were functionally interchangeable with splenic DC. Both hepatic accessory cells (AC) and splenic DC adhere firmly to plastic culture dishes or wells within 2 hr; but hepatic AC, unlike splenic DC, do not detach during 22 hr additional incubation. Hepatic AC, unlike splenic DC, are not lysed or inactivated by monoclonal antibody 33D1 and C'. Hepatic AC and splenic DC are similarly sensitive to irradiation in vivo and insensitive to irradiation in vitro. Hepatic AC are separated with cells which are predominantly phagocytic and FcR+ and contain nonspecific esterase. Both hepatic AC and splenic DC are suppressed or eliminated by activation of NK cells in vivo, a phenomenon prevented by prior elimination of NK cells.


Assuntos
Células Apresentadoras de Antígenos/imunologia , Células Dendríticas/imunologia , Fígado/citologia , Baço/citologia , Animais , Anticorpos Monoclonais/imunologia , Células Produtoras de Anticorpos/imunologia , Células Apresentadoras de Antígenos/efeitos da radiação , Antígenos de Diferenciação/análise , Adesão Celular , Células Matadoras Naturais/imunologia , Teste de Cultura Mista de Linfócitos , Camundongos , Receptores Fc/análise
8.
Cell Immunol ; 104(2): 440-5, 1987 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-3815537

RESUMO

Both dendritic cells (DC) and macrophages (M phi) stimulate lymphocyte proliferation in secondary mixed-lymphocyte (ML) reactions, though DC are approximately fourfold more effective. Natural killer (NK) cells suppress secondary ML reactions when DC are used, but NK cells do not suppress when M phi are used in these reactions. The findings are consistent with the idea that DC, but not M phi, are potential targets in immune regulation mediated by NK cells.


Assuntos
Células Dendríticas/imunologia , Células Matadoras Naturais/imunologia , Macrófagos/imunologia , Animais , Células Apresentadoras de Antígenos/imunologia , Tolerância Imunológica , Memória Imunológica , Ativação Linfocitária , Camundongos
9.
J Immunol ; 136(10): 3567-71, 1986 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-2871105

RESUMO

Cells highly enriched for natural killer activity suppress the generation of Lyt-2+ cytolytic T cells in one-way mixed lymphocyte cultures. Suppression occurs because natural killer cells suppress or eliminate dendritic cells, which are required for proliferation of both Ly-1+ and Lyt-2+ lymphocytes.


Assuntos
Células Apresentadoras de Antígenos/imunologia , Células Matadoras Naturais/imunologia , Linfócitos T Citotóxicos/imunologia , Animais , Antígenos Ly/análise , Antígenos de Superfície/análise , Células Cultivadas , Citotoxicidade Imunológica , Feminino , Tolerância Imunológica , Imunidade Celular , Interleucina-2/imunologia , Camundongos , Antígenos Thy-1
10.
J Exp Med ; 163(4): 1012-7, 1986 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-3485171

RESUMO

Cells enriched for NK activity (poly I:C induced, x-ray resistant, and nonadherent), include two phenotypically and functionally different populations. Both populations of NK cells are AGM1+, Ly-1.1-, Ly-2.1-, Ia-, and have the morphology of large granular lymphocytes. One population, however, is Thy-1+ while the second population is Thy-1-. Thy-1+ NK cells lyse YAC-1 and P815 target cells; Thy-1- NK cells lyse YAC-1 but not P815 target cells. The FACS was used to obtain homogeneous populations of Thy-1+ and Thy-1- NK cells, which retain high cytotoxicity. While Thy-1- NK cells suppress the antibody response in vitro by suppressing or eliminating DC, Thy-1+ NK cells do not suppress antibody responses in vitro.


Assuntos
Células Matadoras Naturais/imunologia , Animais , Formação de Anticorpos , Linfócitos B/imunologia , Células da Medula Óssea , Separação Celular , Células Matadoras Naturais/classificação , Camundongos
11.
J Immunol ; 136(6): 1974-81, 1986 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-2936817

RESUMO

This paper describes an L3T4+, Lyt-2- cloned T cell line of CBA/N origin that is specific for IEk-encoded products. Splenic dendritic cells are the predominant stimulatory populations for Lbd cells, being approximately 100 times more effective than large activated B cells. Small B cells and T cells are nonstimulatory. Lbd cells help large B cells to make polyclonal antibody responses, but are unable to activate small B cells and to replace antigen-specific helper T cells in T cell-dependent responses to phosphorylcholine or sheep red blood cells. In the presence of antigen-specific helper T cells, Lbd can amplify, suppress, or contrasuppress T cell function, depending on the type and relative ratios of antigen-reactive cells. We explain our findings as a consequence of the self reactivity among helper T cells.


Assuntos
Linfócitos B/imunologia , Antígenos de Histocompatibilidade/imunologia , Tolerância Imunológica , Linfócitos T/imunologia , Animais , Anticorpos Monoclonais/imunologia , Formação de Anticorpos , Antígenos de Diferenciação de Linfócitos T , Antígenos Ly/análise , Antígenos de Superfície/análise , Células Clonais/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Memória Imunológica , Ativação Linfocitária , Complexo Principal de Histocompatibilidade , Camundongos , Camundongos Endogâmicos , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia
12.
Immunol Today ; 7(7-8): 196-8, 1986.
Artigo em Inglês | MEDLINE | ID: mdl-25290396

RESUMO

In this article Donald Rowley and Prakash Shah propose that Thy-1(-) natural killer (NK) cells activated during the course of immune reactions suppress or eliminate dendritic cells (DC) which have interacted with antigen and are required to stimulate lymphocyte proliferation. They review the experimental basis for this concept of immune regulation and emphasize that nearly homogeneous populations of well-characterized NK cells are required to define the functions of NK cells.

13.
J Exp Med ; 162(2): 625-36, 1985 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-3160806

RESUMO

Natural killer (NK) cells (poly I:C induced, x-ray resistant, nonadherent, Thy-1-, Ly-1.1-, Ly-2.1-, anti-asialo GM1-positive, and cytotoxic for YAC-1) suppressed T lymphocyte proliferation in mixed lymphocyte reaction (MLR) and autologous MLR cultures. Dendritic cells (DC) were required for proliferation of lymphocytes in both responses. The question whether lymphocytes or DC were the targets for NK cells was resolved by taking advantage of the fact that NK cells, but not DC, lose activity after 24 h in culture. Three findings indicate that DC, not lymphocytes, are targets for NK cells. First, responses suppressed by NK cells were fully restored by adding small numbers of DC to cultures 24 h after NK cells had been added. Second, DC incubated alone with NK cells and antigen for 24 h did not stimulate proliferation of lymphocytes. Third, lymphocytes incubated alone with NK cells for 24 h proliferated normally when DC were added. Additional experiments showed that DC became targets only after interaction with antigen. Thus, we suggest that NK cells may regulate lymphocyte proliferation by monitoring antigen presentation by DC.


Assuntos
Células Apresentadoras de Antígenos/imunologia , Antígenos/imunologia , Células Matadoras Naturais/imunologia , Animais , Comunicação Celular , Meios de Cultura , Citotoxicidade Imunológica , Ativação Linfocitária , Teste de Cultura Mista de Linfócitos , Camundongos , Camundongos Endogâmicos , Linfócitos T/imunologia
14.
Am J Cardiol ; 44(7): 1383-90, 1979 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-506941

RESUMO

Seventeen patients with accepted M mode echocardiographic criteria for flail mitral leaflet were studied. M mode echocardiograms revealed characteristic disordered mitral valve motion: (1) 16 (94 percent) had chaotic diastolic mitral motion; (2) 14 (82 percent) had systolic mitral flutter; (3) 14 (82 percent) had systolic left atrial echoes; and (4) 12 (71 percent) had systolic mitral valve prolapse. In 8 patients (47 percent) all four findings were present, with three findings present in 16 (35 percent) and two findings present in 13 (18 percent); none had fewer than two findings. Cross-sectional echocardiographic studies in 10 patients revealed a systolic whipping motion of the posterior mitral leaflet into the left atrium in all, abnormal systolic mitral coaptation in all and an abnormal mass of systolic left atrial echoes in 4. None of the first three M mode criteria were observed in 230 patients with uncomplicated "mid systolic click-late systolic murmur" syndrome; cross-sectional echocardiography in 30 of 230 patients revealed normal systolic mitral coaptation and no systolic whipping of the tip of the posterior mitral leaflet into the left atrium.


Assuntos
Ecocardiografia , Insuficiência da Valva Mitral/diagnóstico , Adolescente , Adulto , Idoso , Diástole , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/etiologia , Prolapso da Valva Mitral/diagnóstico , Sístole
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