Role of CD5/CD5L interactions in the homeostasis of regulatory lymphocyte subpopulations and the control of autoimmune disorders

Resumen del trabajo presentado al: "6th European Workshop on Immune-Mediated Inflammatory Diseases" celebrado en Niza (Francia) del 23 al 25 de noviembre de 2011.-- et al.Peer Reviewe

Transgenic Expression of Soluble Human CD5 Enhances Experimentally-Induced Autoimmune and Anti-Tumoral Immune Responses

CD5 is a lymphoid-specific transmembrane glycoprotein constitutively expressed on thymocytes and mature T and B1a lymphocytes. Current data support the view that CD5 is a negative regulator of antigen-specific receptor-mediated signaling in these cells, and that this would likely be achieved through interaction with CD5 ligand/s (CD5L) of still undefined nature expressed on immune or accessory cells. To determine the functional consequence of loss of CD5/CD5L interaction in vivo, a new transgenic mouse line was generated (shCD5EμTg), expressing a circulating soluble form of human CD5 (shCD5) as a decoy to impair membrane-bound CD5 function. These shCD5EμTg mice showed an enhanced response to autologous antigens, as deduced from the presentation of more severe forms of experimentally inducible autoimmune disease (collagen-induced arthritis, CIA; and experimental autoimmune encephalitis, EAE), as well as an increased anti-tumoral response in non-orthotopic cancer models (B16 melanoma). This enhancement of the immune response was in agreement with the finding of significantly reduced proportions of spleen and lymph node Treg cells (CD4+CD25+FoxP3+), and of peritoneal IL-10-producing and CD5+ B cells, as well as an increased proportion of spleen NKT cells in shCD5EμTg mice. Similar changes in lymphocyte subpopulations were observed in wild-type mice following repeated administration of exogenous recombinant shCD5 protein. These data reveal the relevant role played by CD5/CD5L interactions on the homeostasis of some functionally relevant lymphocyte subpopulations and the modulation of immune responses to autologous antigens

John Soane’s House in London (1792-1827). Light, Lighting and Heritage

La denominada Casa-museo de Sir John Soane en Londres (1792-1837), es uno de los edificios singulares en la historia de la arquitectura tanto por la metamorfosis que sufrió de casa-estudio a museo como por el uso excepcional de la luz natural y la iluminación que se produjo en su interior. El arquitecto y habitante creó ambientes únicos en sus habitaciones, construyendo atmósferas evocadoras mediante el sabio tratamiento de la luz natural y a través de una escenográfica propuesta de iluminación artificial. Esta síntesis de una más amplia investigación reivindica la luz y la iluminación como valores que debieran formar parte de los argumentos utilizados para considerar cualquier arquitectura como patrimonio al tiempo que razona porqué su análisis es imprescindible para proyectar el comportamiento de la luz y la iluminación en las propuestas contemporáneas de intervención en el patrimonio.The Sir John Soane´s House-museum in London (1792-1837), is one of the unique domestic buildings in the history of architecture because of its metamorphosis from house-studio to museum as well as the outstanding use of natural light and lighting in its interiors. The architect and inhabitant created unique atmospheres in the different rooms, constructing evocative ambiances through the wise use of natural light and through the scenic proposal of artificial lighting. This synthesis of a broader research claims light and lighting as values that should be part of the arguments used to consider a certain architecture as heritage while explaining why its analysis is essential to design the light and lighting of the contemporary intervention projects in heritage

John Soane’s House in London (1792-1827). Light, Lighting and Heritage

La denominada Casa-museo de Sir John Soane en Londres (1792-1837), es uno de los edificios singulares en la historia de la arquitectura tanto por la metamorfosis que sufrió de casa-estudio a museo como por el uso excepcional de la luz natural y la iluminación que se produjo en su interior. El arquitecto y habitante creó ambientes únicos en sus habitaciones, construyendo atmósferas evocadoras mediante el sabio tratamiento de la luz natural y a través de una escenográfica propuesta de iluminación artificial. Esta síntesis de una más amplia investigación reivindica la luz y la iluminación como valores que debieran formar parte de los argumentos utilizados para considerar cualquier arquitectura como patrimonio al tiempo que razona porqué su análisis es imprescindible para proyectar el comportamiento de la luz y la iluminación en las propuestas contemporáneas de intervención en el patrimonio.The Sir John Soane´s House-museum in London (1792-1837), is one of the unique domestic buildings in the history of architecture because of its metamorphosis from house-studio to museum as well as the outstanding use of natural light and lighting in its interiors. The architect and inhabitant created unique atmospheres in the different rooms, constructing evocative ambiances through the wise use of natural light and through the scenic proposal of artificial lighting. This synthesis of a broader research claims light and lighting as values that should be part of the arguments used to consider a certain architecture as heritage while explaining why its analysis is essential to design the light and lighting of the contemporary intervention projects in heritage

Analysis of total cell numbers in primary and secondary lymphoid organs from shCD5EμTg mice.

<p>Total number of mononuclear cells in spleen, thymus, bone marrow, lymph node and peritoneal lavage samples was measured by flow cytometry using forward and side scatter for gating. ** p = 0.0018.</p