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PLoS One. 2014 Jan 15;9(1):e84895. doi: 10.1371/journal.pone.0084895. eCollection 2014.

Transgenic expression of soluble human CD5 enhances experimentally-induced autoimmune and anti-tumoral immune responses.

Author information

1
Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
2
Departamento de Biología Molecular, Universidad de Cantabria, Santander, Spain.
3
Servei de Malalties Autoimmunes Sistémiques, Hospital Clínic de Barcelona, Barcelona, Spain.
4
Departament de Biologia Cel·lular, Immunologia i Neurociències, Universitat de Barcelona, Barcelona, Spain.
5
Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
6
Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
7
Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America.
8
Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Distrito Federal, México.
9
Departamento de Biología Molecular, Universidad de Cantabria, Santander, Spain ; Instituto de Biomedicina y Biotecnología de Cantabria, Consejo Superior de Investigaciones Científicas-Universidad de Cantabria-SODERCAN, Santander, Spain.
10
Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain ; Departament de Biologia Cel·lular, Immunologia i Neurociències, Universitat de Barcelona, Barcelona, Spain ; Servei d'Immunologia, Hospital Clínic de Barcelona, Barcelona, Spain.

Abstract

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.

PMID:
24454761
PMCID:
PMC3893160
DOI:
10.1371/journal.pone.0084895
[Indexed for MEDLINE]
Free PMC Article
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