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.
Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Rafael
R
Fenutría
Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Vanesa G
VG
Martinez
Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Inês
I
Simões
Departamento de Biología Molecular, Universidad de Cantabria, Santander, Spain.
Jorge
J
Postigo
Servei de Malalties Autoimmunes Sistémiques, Hospital Clínic de Barcelona, Barcelona, Spain.
Victor
V
Gil
Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Mario
M
Martínez-Florensa
Departament de Biologia Cel·lular, Immunologia i Neurociències, Universitat de Barcelona, Barcelona, Spain.
Jordi
J
Sintes
Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Rodrigo
R
Naves
Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Kevin S
KS
Cashman
Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America.
José
J
Alberola-Ila
Servei de Malalties Autoimmunes Sistémiques, Hospital Clínic de Barcelona, Barcelona, Spain.
Manel
M
Ramos-Casals
Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Distrito Federal, México.
Gloria
G
Soldevila
Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Chander
C
Raman
Departamento de Biología Molecular, Universidad de Cantabria, Santander, Spain.
Jesús
J
Merino
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.
Ramón
R
Merino
Departament de Biologia Cel·lular, Immunologia i Neurociències, Universitat de Barcelona, Barcelona, Spain.
Pablo
P
Engel
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.
Francisco
F
Lozano
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D001483:Base Sequence; D018956:CD5 Antigens / Q000235:genetics / Q000276:immunology*; D017931:DNA Primers; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology*; D016133:Polymerase Chain Reaction
D018956:CD5 Antigens; D017931:DNA Primers