title: Th17 differentiation is the default program for DPP2-deficient T-cell differentiation.
abstract: Dipeptidyl peptidase 2 (DPP2) is an N-terminal dipeptidase, required for maintaining lymphocytes in a resting state. Mutant mice with T-cell-specific knock-down (kd) of DPP2 (lck-DPP2 kd) were generated and analyzed for their phenotype. Normal thymocyte development and a modest increase in the proportions of peripheral T cells were observed in these mice compared with littermate controls. Interestingly, the peripheral T cells were hyperactive upon TCR stimulation in vitro, although they did not express any activation markers. Furthermore, CD3-crosslinking in the naïve CD4(+) and CD8(+) T cells of lck-DPP2 kd mice resulted mainly in IL-17 production. Similarly, the mutant T cells secreted primarily IL-17 after in vivo priming and in vitro antigen-specific restimulation. These data suggest that IL-17 production is the default program for T-cell differentiation in the absence of DPP2. Thus, DPP2 seems to impose a threshold for quiescent T cells, preventing them from drifting into cell cycle.
authors.affiliation: Graduate Program in Cell and Molecular Physiology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Deanna A
authors.initials: DA
authors.lastname: Mele
authors.forename: James F
authors.initials: JF
authors.lastname: Sampson
authors.forename: Brigitte T
authors.initials: BT
authors.lastname: Huber
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007114:Immunization; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D017252:CD3 Complex; D020381:Interleukin-17; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C100151:dipeptidyl peptidase II