title: Allogeneic induced human FOXP3(+)IFN-gamma(+) T cells exhibit selective suppressive capacity.
abstract: Human induced CD4(+)CD25(+) T cells have been shown to express FOXP3, similar to naturally occurring Treg cells (nTreg). However, the suppressive capacity of these cells is still under debate. The current study was designed to investigate functional characteristics of CD25(+)FOXP3(+) derived from CD25(-) T cells. Stimulation of CD25(-) PBMC with allogeneic PBMC resulted in production of CD4(+)CD25(high) T cells. This process was more rapid and prominent when highly mature DC were used for stimulation. The resultant CD4(+)CD25(high) population concurrently exhibited regulatory markers FOXP3, CTLA-4, GITR, and inflammatory cytokines IL-2 and IFN-gamma. These human-induced FOXP3(+)IFN-gamma(+) T cells were shown, for the first time, to markedly inhibit alloreactive T-cell expansion, similar to nTreg. However, in contrast to nTreg, the induced CD4(+)CD25(+)FOXP3(+) cells did not suppress proliferation against a third party donor stimulus or CMV. This suggested that the cell population possessed a more selective suppressive capacity targeted against the original stimulus only. The induced human CD4(+)CD25(+)FOXP3(+) subset derived from CD25(-) T cells, while expressing inflammatory cytokines, exhibits a suppressive cell contact-dependent effect, restricted against T cells responding to the original stimulus. Such unique properties suggest that these cells are potentially ideal for the use as post-transplant GVH disease prophylaxis.
authors.affiliation: Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: Dina
authors.initials: D
authors.lastname: Stroopinsky
authors.forename: Irit
authors.initials: I
authors.lastname: Avivi
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Rowe
authors.forename: David
authors.initials: D
authors.lastname: Avigan
authors.forename: Tamar
authors.initials: T
authors.lastname: Katz
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D060908:CTLA-4 Antigen; D002450:Cell Communication / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D016753:Interleukin-10 / Q000494:pharmacology; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D000098815:T-bet Transcription Factor
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053450:Glucocorticoid-Induced TNFR-Related Protein; C508609:IL10 protein, human; C508017:IL2RA protein, human; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C491405:TNFRSF18 protein, human; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma