Identification of novel immunoregulatory molecules in human thymic regulatory CD4+CD25+ T cells by phage display

Thymic CD4+CD25+ cells play an important role in immune regulation and are continuously developed in the thymus as an independent lineage. How these cells are generated, what are their multiple pathways of suppressive activity and which are their specific markers are questions that remain unanswered...

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Bibliographic Details
Published in:PloS one 2011-08, Vol.6 (8), p.e21702-e21702
Main Authors: Porto, Georgia, Giordano, Ricardo J, Marti, Luciana C, Stolf, Beatriz, Pasqualini, Renata, Arap, Wadih, Kalil, Jorge, Coelho, Verônica
Format: Article
Language:English
Subjects:
Antigens
Autoimmune diseases
Bacteriophages - genetics
Binding
Biology
Cancer
CD25 antigen
CD4 antigen
CD4 Antigens - immunology
Chemistry
Children & youth
Cytokines
Dendritic cells
Endocrine system
Enzyme-Linked Immunosorbent Assay
Families & family life
Flow Cytometry
Forkhead Transcription Factors - immunology
Heart
Humans
Immune system
Immunology
Immunoregulation
Interleukin-2 Receptor alpha Subunit - immunology
Libraries
Ligands
Lymphocytes
Lymphocytes T
Medicine
Ontogeny
Peptides
Phage display
Phages
Receptors, Calcitriol - immunology
T cell receptors
T-Lymphocytes - immunology
Thymocytes
Thymus
Thymus Gland - immunology
Transcription factors
Vitamin D
Vitamin D receptors
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Summary:Thymic CD4+CD25+ cells play an important role in immune regulation and are continuously developed in the thymus as an independent lineage. How these cells are generated, what are their multiple pathways of suppressive activity and which are their specific markers are questions that remain unanswered. To identify molecules involved in the function and development of human CD4+CD25+ T regulatory cells we targeted thymic CD4+CD25+ cells by peptide phage display. A phage library containing random peptides was screened ex vivo for binding to human thymic CD4+CD25+ T cells. After four rounds of selection on CD4+CD25+ enriched populations of thymocytes, we sequenced several phage displayed peptides and selected one with identity to the Vitamin D Receptor (VDR). We confirmed the binding of the VDR phage to active Vitamin D in vitro, as well as the higher expression of VDR in CD4+CD25+ cells. We suggest that differential expression of VDR on natural Tregs may be related to the relevance of Vitamin D in function and ontogeny of these cells.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0021702