Chronic antigen stimulation in vivo induces a distinct population of antigen-specific Foxp3 CD25 regulatory T cells.
The concept of immune regulation/suppression has been well-established and, besides thymus-derived CD4+CD25+ regulatory T (TR) cells, it became clear that a variety of additional peripherally induced TR cells play vital roles in protection from many harmful immune responses including intestinal inflammation. In the present study, we have analyzed in vivo-induced Ag-specific CD4+ TR cells with respect to their molecular and functional phenotype. By comparative genomics we could show that these Ag-specific TR cells induced by chronic Ag stimulation in vivo clearly differ in their genetic program from naturally occurring thymus-derived CD4+CD25+ TR cells. This distinct population of induced TR cells express neither CD25 nor the TR-associated transcription factor Foxp3. Strikingly, CD25 is not even up-regulated upon stimulation. Despite the lack in Foxp3 expression, these in vivo-induced CD25- TR cells are able to interfere with an Ag-specific CD8+ T cell-mediated intestinal inflammation without significant increase in CD25 and Foxp3 expression. Thus, our results demonstrate that in vivo-induced Ag-specific TR cells represent a distinct population of Foxp3-CD25- TR cells with regulatory capacity both in vitro and in vivo.
Hansen
Wiebke
W
Institute of Medical Microbiology, University Hospital Essen, Essen, Germany. wiebke.hansen@uk-essen.de
Westendorf
Astrid M
AM
Reinwald
Simone
S
Bruder
Dunja
D
Deppenmeier
Stefanie
S
Groebe
Lothar
L
Probst-Kepper
Michael
M
Gruber
Achim D
AD
Geffers
Robert
R
Buer
Jan
J
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000032:analysis* / Q000235:genetics; D020869:Gene Expression Profiling; D023281:Genomics; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis* / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000956:Antigens, Viral; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D053645:Interleukin-2 Receptor alpha Subunit