Regulatory T cells and dendritic cells in transplantation tolerance: molecular markers and mechanisms.
Transplantation tolerance can be induced in adult rodents using monoclonal antibodies against coreceptor or costimulation molecules on the surface of T cells. There are currently two well-characterized populations of T cells, demonstrating regulatory capacity: the "natural" CD4+CD25+ T cells and the interleukin (IL)-10-producing Tr1 cells. Although both types of regulatory T cells can induce transplantation tolerance under appropriate conditions, it is not clear whether either one plays any role in drug-induced dominant tolerance, primarily due to a lack of clear-cut molecular or functional markers. Similarly, although dendritic cells (DCs) can be pharmacologically manipulated to promote tolerance, the phenotype of such populations remains poorly defined. We have used serial analysis of gene expression (SAGE) with 29 different T-cell and antigen-presenting cell libraries to identify gene-expression signatures associated with immune regulation. We found that independently derived, regulatory Tr1-like clones were highly concordant in their patterns of gene expression but were quite distinct from CD4+CD25+ regulatory T cells from the spleen. DCs that were treated with the tolerance-enhancing agents IL-10 or vitamin D3 expressed a gene signature reflecting a functional specification in common with the most immature DCs derived from embryonic stem cells.
Cobbold
Stephen P
SP
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. stephen.cobbold@path.ox.ac.uk
Nolan
Kathleen F
KF
Graca
Luis
L
Castejon
Raquel
R
Le Moine
Alain
A
Frewin
Mark
M
Humm
Susan
S
Adams
Elizabeth
E
Thompson
Sara
S
Zelenika
Diana
D
Paterson
Alison
A
Yates
Stephen
S
Fairchild
Paul J
PJ
Waldmann
Herman
H
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D023001:Transplantation Tolerance / Q000276:immunology*
D015703:Antigens, CD