Matured human monocyte-derived dendritic cells (MoDCs) induce expansion of CD4+CD25+FOXP3+ T cells lacking regulatory properties.
Naturally occurring CD4(+)CD25(+) T regulatory cells (nTregs) play a key role as suppressors in immune mechanisms that protect against self-destruction. The forkhead box p3 transcription factor (FOXP3) has a central role in the development of nTregs. We show here that co-culture of naïve T cells with flagellin-exposed monocyte-derived dendritic cells (MoDCs) generates CD4(+)CD25(+)FOXP3(+) T cells that transiently express FOXP3 together with CD25 but do not suppress proliferation of CD4(+)CD25(-) T cells. Moreover, purified CD4(+)CD25(+)FOXP3(+) T cells reveal a different proliferation and cytokine production profile from that of nTregs. These data indicate that in the presence of ongoing immune responses a T cell antigenic phenotype superimposable of that of nTregs does not necessarily predict suppressive function and that FOXP3 in humans is not sufficient for development and function of regulatory T cells.
Merlo
Andrea
A
Molecular Biology Unit, Department of Experimental Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy. Andrea.Merlo@istitutotumori.mi.it
Tagliabue
Elda
E
Mènard
Sylvie
S
Balsari
Andrea
A
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005408:Flagellin / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis / Q000378:metabolism; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D005408:Flagellin