Suppressive dendritic cells as a tool for controlling allograft rejection in organ transplantation: Promises and difficulties

Ehser, Sandra; Chuang, Jing Jing; Kleist, Christian; Șandra-Petrescu, Flavius; Iancu, Mircea; Wang, Daohu; Opelz, Gerhard; Terness, Peter

doi:10.1016/j.humimm.2008.01.018

Cited by 22 publications

(18 citation statements)

References 80 publications

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“…En reposo, las pDC pueden clasificarse como prepDC (16), pero una vez se activan, adquieren la capacidad para producir grandes cantidades de interferones de tipo I y pueden presentar algunas propiedades de procesamiento y presentación de antígeno (21,22). Se creía que las células dendríticas derivadas de los precursores mieloides inducían sólo respuestas de tipo Th1, mientras que las de origen linfoide inducían sólo respuestas de tipo Th2, pero se ha demostrado que las pDC de origen linfoide también pueden inducir respuestas de tipo Th1 después de la activación con algunos virus o con CD40 (23,24).…”

Section: Biología De Las Células Dendríticasunclassified

“…Estos tratamientos se basan en el uso de fármacos inmunosupresores que bloquean la activación del sistema inmunitario, conduciendo así a múltiples efectos secundarios, como el incremento de la incidencia y seriedad de infecciones y neoplasias (1). Para minimizar estos efectos, la inmunología de trasplantes se ha enfocado en el estudio de la tolerancia específica de antígeno (2,3).…”

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“…Las células presentadoras de antígeno por excelencia son las células dendríticas, las cuales juegan un papel central en la iniciación de la inmunidad y la tolerancia (2,5). Existen diferentes mecanismos por los cuales estas células pueden inducir tolerancia.…”

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Papel de las células dendríticas tolerogénicas ILT3+/ILT4+ en la respuesta inmunitaria a trasplante de órganos y tejidos

Arboleda¹,

García²,

Álvarez³

2011

biomedica

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Las células dendríticas son las células presentadores de antígeno más potentes y, por lo tanto, son importantes en el desencadenamiento de la respuesta inmunitaria frente a aloantígenos; sin embargo, también juegan un papel fundamental en el mantenimiento de la tolerancia periférica. La tolerancia es potenciada por la expresión en estas células de los receptores inhibidores ILT3 e ILT4, los cuales, mediante el reclutamiento de fosfatasas de tirosinas a sus dominios ITIM, inhiben la activación de la célula presentadora de antígeno y conducen a una débil respuesta de la célula T. Estos receptores propician, además, una interacción bidireccional con células T supresoras, T reguladoras o ambas, generando una cascada inmunorreguladora específica de antígeno, en la cual la célula dendrítica se comporta como una célula "tolerogénica". En esta revisión analizamos la biología y el comportamiento de las células dendríticas tolerogénicas que expresan altos niveles de ILT3 e ILT4, así como algunos aspectos moleculares y genéticos de estos receptores y su importancia en la modulación de las respuestas inmunitarias específicas de aloantígeno frente a un trasplante.Palabras clave: trasplante, células dendríticas, tolerancia inmunológica, inmunomodulación, supervivencia. ILT3 + /ILT4 + tolerogenic dendritic cells and their influence on allograft survivalDendritic cells, the most powerful antigen-presenting cells, are important for triggering of the immune responses to allo-antigens. However, they also play a fundamental role in the peripheral tolerance maintenance. Tolerance is enhanced by the presence on the dendritic cell surface of the inhibitor receptors ILT3 and ILT4. They recruit protein tyrosine-phosphatases to their ITIM domains and inhibit antigen-presenting cell activation, leading T cell hypo-responsivensess. Moreover, these receptors favor a bidirectional interaction with T-suppressor and T-regulator cells, generating an antigen-specific immunoregulator cascade, in which the dendritic cell behaves as a tolerogenic cell. In the current review, analysis is centered on the biology and behavior of the tolerogenic dendritic cells that express high levels of ILT3 and ILT4. Some molecular and genetics aspects of these receptors are discussed as well as their importance in the modulation of the allo-specific antigen immune response to transplants.

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Section: Biología De Las Células Dendríticasunclassified

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Papel de las células dendríticas tolerogénicas ILT3+/ILT4+ en la respuesta inmunitaria a trasplante de órganos y tejidos

Arboleda¹,

García²,

Álvarez³

2011

biomedica

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“…This objective is clinically relevant, as studies modulating DC numbers are in development for the treatment of patients with asthma (30,32), autoimmunity (65,68,74), organ transplantation (12,39,43), and cancer (3,11,73). It is unknown whether manipulating the number of tissue DC will alter the innate or adaptive antifungal host defense in these patients.…”

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Role of Dendritic Cells and Alveolar Macrophages in Regulating Early Host Defense against Pulmonary Infection withCryptococcus neoformans

et al. 2009

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Successful pulmonary clearance of the encapsulated yeast Cryptococcus neoformans requires a T1 adaptive immune response. This response takes up to 3 weeks to fully develop. The role of the initial, innate immune response against the organism is uncertain. In this study, an established model of diphtheria toxin-mediated depletion of resident pulmonary dendritic cells (DC) and alveolar macrophages (AM) was used to assess the contribution of these cells to the initial host response against cryptococcal infection. The results demonstrate that depletion of DC and AM one day prior to infection results in rapid clinical deterioration and death of mice within 6 days postinfection; this effect was not observed in infected groups of control mice not depleted of DC and AM. Depletion did not alter the microbial burden or total leukocyte recruitment in the lung. Mortality (in mice depleted of DC and AM) was associated with increased neutrophil and B-cell accumulation accompanied by histopathologic evidence of suppurative neutrophilic bronchopneumonia, cyst formation, and alveolar damage. Collectively, these data define an important role for DC and AM in regulating the initial innate immune response following pulmonary infection with C. neoformans. These findings provide important insight into the cellular mechanisms which coordinate early host defense against an invasive fungal pathogen in the lung.Cryptococcus neoformans, an opportunistic fungal pathogen acquired through inhalation, causes significant morbidity and mortality primarily in patients with impairments in host defense, including those with AIDS, those with lymphoid or hematological malignancies, or those receiving immunosuppressive therapy secondary to autoimmune disease or organ transplantation (31,33,60). The development of a T1 antigenspecific immune response characterized by gamma interferon production and classical activation of macrophages is required to eradicate the organism (4,8,21,23,24,28). This adaptive immune response takes 2 to 3 weeks to develop and coincides with the CCR2-mediated recruitment of additional pulmonary dendritic cells (DC) and T cells to the lung (51,66,67). The role of initial, innate immune responses against the organism (prior to the development of adaptive immunity) is not well understood.Resident lung phagocytic cells, primarily DC and alveolar macrophages (AM), are likely the first immune cells exposed to C. neoformans upon inhalation of the organism into the lung. Both DC and AM express lectin receptors, including macrophage mannose receptor and DC-specific non-ICAM3 grabbing nonintergrin (DC-SIGN) (14, 15), which bind C. neoformans glycoantigens, including mannoproteins (42, 55). DC and AM phagocytose the organism in vitro and in vivo (29,34,63,77,78), and phagocytosis (and/or exposure to soluble glycoantigens or cryptococcal DNA) is associated with cytokine and chemokine production (5,29,40,48,49,55,61) and yeast lysis (77). It is unclear whether phagocytosis by resident DC and AM contributes to early clearance and/or the la...

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“…In addition, DC binding and transmigration on allogenic ECs exposed to calcineurin inhibitors were concentration-dependently increased, indicating that long-term immunosuppression mediates enhanced invasion of DCs to the donor organ and aggravates chronic rejection [90] . Furthermore, DCs have been used as tools for controlling allograft rejection in organ transplantation [91,92] . Shlomchik et al [93] provided evidence of prevention of graft versus host disease by inactivation of host antigen-presenting cells.…”

Section: Dcs and Cardiac Transplantationmentioning

confidence: 99%

Role of dendritic cells in cardiovascular diseases

Zhang¹

2010

WJC

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Dendritic cells (DCs) are potent antigen-presenting cells that bridge innate and adaptive immune responses. Recent work has elucidated the DC life cycle, including several important stages such as maturation, migration and homeostasis, as well as DC classification and subsets/locations, which provided etiological insights on the role of DCs in disease processes. DCs have a close relationship to endothelial cells and they interact with each other to maintain immunity. DCs are deposited in the atherosclerotic plaque and contribute to the pathogenesis of atherosclerosis. In addition, the necrotic cardiac cells induced by ischemia activate DCs by Tolllike receptors, which initiate innate and adaptive immune responses to renal, hepatic and cardiac ischemia reperfusion injury (IRI). Furthermore, DCs are involved in the acute/chronic rejection of solid organ transplantation and mediate transplant tolerance as well. Advancing our knowledge of the biology of DCs will aid development of new approaches to treat many cardiovascular diseases, including atherosclerosis, cardiac IRI and transplantation.

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Suppressive dendritic cells as a tool for controlling allograft rejection in organ transplantation: Promises and difficulties

Cited by 22 publications

References 80 publications

Papel de las células dendríticas tolerogénicas ILT3+/ILT4+ en la respuesta inmunitaria a trasplante de órganos y tejidos

Papel de las células dendríticas tolerogénicas ILT3+/ILT4+ en la respuesta inmunitaria a trasplante de órganos y tejidos

Role of Dendritic Cells and Alveolar Macrophages in Regulating Early Host Defense against Pulmonary Infection withCryptococcus neoformans

Role of dendritic cells in cardiovascular diseases

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