Modified myeloid dendritic cells act as regulatory dendritic cells to induce anergic and regulatory T cells

Liu

The Journal of Immunology

et al. 2006

The ability of dendritic cells (DC) to initiate immune responses or induce immune tolerance is strictly dependent on their maturation state. TNF-α plays a pivotal role in the differentiation and maturation of DC. Blockade of TNF-α action may arrest DC in an immature state, prolonging their window of tolerogenic opportunity. Immature DC (imDC) were transfected with recombinant adenovirus to express soluble TNF-α receptor type I (sTNFRI), a specific inhibitor of TNF-α. The capacity of sTNFRI gene-modified imDC (DC-sTNFRI) to induce immune tolerance was analyzed. sTNFRI expression renders imDC resistant to maturation induction and impairs their capacity to migrate or present Ag. This process leads to induction of allogeneic T cell hyporesponsiveness and the generation of IL-10-producing T regulatory-like cells. In vivo pretreatment of transplant recipients with DC-sTNFRI induces long-term survival of cardiac allografts in 50% of cases, and leads to a substantial increase in the generation of microchimerism and T regulatory cell numbers. Thus, blockade of TNF-α action by sTNFRI genetic modification can inhibit the maturation of DC and potentiate the in vivo capacity of imDC to induce donor-specific immune tolerance and prolong allograft survival.

Section: Discussionsupporting

confidence: 82%

Section: Analysis Of Tregs In Vitro and In Vivomentioning

confidence: 99%

Induction of Allospecific Tolerance by Immature Dendritic Cells Genetically Modified to Express Soluble TNF Receptor

Liu

The Journal of Immunology

et al. 2006

“…Tienen una gran capacidad endocítica y expresan una variedad de receptores para la captura de antígenos, incluyendo FcgRs, CD32 y CD64, los receptores de IgE FcεRI y FcεRII, los receptores del complemento CD11b y CD11c, DEC205, un receptor de unión a manosa de tipo lectina-C, variedad de receptores de tipo toll o TLR, la molécula DC-SIGN (Dendritic Cell-Specific Intercellular Adhesion Molecule-3-Grabbing Non-Integrin) o CD209 y receptores scavenger para células apoptóticas como α v β 5 y CD36 (25). Durante el proceso de maduración, estos receptores les permiten a las células dendríticas capturar eficientemente todo tipo de antígenos, tales como bacterias, virus, células muertas, proteínas y complejos inmunitarios, para procesar las proteínas y convertirlas en péptidos (26)(27)(28).…”

Section: Biología De Las Células Dendríticasunclassified

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

Arboleda¹,

García²,

Álvarez³

2011

biomedica

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.

The Journal of Immunology

“…In addition, DC can exert potent immunoregulatory effects on T cells (3)(4)(5). Therefore, proteins that are induced upon DC differentiation can be considered candidates for molecules with costimulatory or inhibitory properties.…”

Section: Molecular Characterization Of Human 4ig-b7-h3 a Member Of Tmentioning

confidence: 99%

“…I n vitro differentiation of monocytes toward dendritic cells (DC) 3 results in a dramatic increase in their immune stimulatory capacity (1,2). In addition, DC can exert potent immunoregulatory effects on T cells (3)(4)(5).…”

Section: Molecular Characterization Of Human 4ig-b7-h3 a Member Of Tmentioning

confidence: 99%

Molecular Characterization of Human 4Ig-B7-H3, a Member of the B7 Family with Four Ig-Like Domains

Schmitz

Majdic

Derdak

et al. 2004

235

266

In an effort to characterize molecules with immunoregulatory potential, we raised mAbs to human dendritic cells. We selected an Ab that recognizes a molecule that is induced on monocytes differentiated in vitro toward dendritic cells. Retroviral expression cloning identified this molecule as B7-H3, a member of the B7 family described recently. In contrast to an earlier report, in which B7-H3 was described as a molecule consisting of two Ig-like domains, our cDNA encoded a type I membrane protein with four Ig-like domains, and the molecule identified by us was therefore named 4Ig-B7-H3. mRNA analysis as well as Western blotting experiments performed by us did not reveal evidence for a small B7-H3. B7-H3 is not expressed on peripheral blood lymphocytes, monocytes, or granulocytes. Upon in vitro stimulation, the expression of B7-H3 is induced on T cells, B cells, and NK cells. A number of different approaches were used to investigate the function of human B7-H3. In contrast to an earlier report, our data do not support a costimulatory role of B7-H3 in anti-CD3-mediated activation of the TCR-complex resulting in T cell proliferation and IFN-γ production.