Alloantigen-specific de novo-induced Foxp3+ Treg revert in vivo and do not protect from experimental GVHD.
Induced antigen-specific Foxp3(+) T cells (iTreg) are being discussed as a promising alternative to polyclonal natural Foxp3(+) T cells (nTreg) for cell-based therapies, particularly to achieve transplantation tolerance. Using Foxp3eGFP-reporter mice, we here establish an efficient protocol to induce and expand alloantigen-specific iTreg from Foxp3(-)CD4(+) T cells with cluster-disrupted DC. These iTreg were mainly CD62L(+) and showed efficient suppressive activity in vitro. However, in contrast to nTreg, adoptively transferred iTreg entirely failed to prevent lethal graft versus host disease (GVHD). Within irradiated recipients, the majority of adoptively transferred Foxp3(+) iTreg, but not Foxp3(+) nTreg quickly reverted to Foxp3(-)CD4(+) T cells. We therefore suggest that therapeutic approaches to treat GVHD should rely on nTreg, whereas the use of de novo alloantigen-induced iTreg should be handled with caution since the stability of the regulatory phenotype of the iTreg could be of major concern.
Koenecke
Christian
C
Institute of Immunology, Hannover Medical School, Hannover, Germany.
Czeloth
Niklas
N
Bubke
Anja
A
Schmitz
Susanne
S
Kissenpfennig
Adrien
A
Malissen
Bernard
B
Huehn
Jochen
J
Ganser
Arnold
A
Förster
Reinhold
R
Prinz
Immo
I
D019264:Adoptive Transfer; D000818:Animals; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation; D023001:Transplantation Tolerance / Q000276:immunology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007519:Isoantigens