Figure 6.
DU-14 induces PTP1B and TC-PTP degradation in CD8+ naïve T cells, enhances STAT1 and STAT5 phosphorylation, and promotes CD8+ T cell activation. (A) Purified CD8+ naïve T cells from control (Ptpn2fl/fl) and Lck-Cre; Ptpn2fl/fl mice (n=3/genotype/condition) were incubated for 48 h with IL-7 in the presence or absence of DU-14 as indicated and TC-PTP and PTP1B protein levels monitored by flow cytometry. (B-C) Vehicle-treated control, TCPTP-deficient Lck-Cre; Ptpn2fl/fl and DU-14-treated control naïve CD8+ T cells were stimulated with plate-bound α-CD3/α-CD28 for 48 h to promote T cell activation. (B) Basal STAT-1 (p(Y701) STAT-1) and STAT-5 (p(Y694) STAT-5) phosphorylation were assessed by flow cytometry. (C) Cell size (FSC-A) and the T cell activation markers CD25, CD69 and CD44 (MFI; mean fluorescence intensities) were measured by flow cytometry. (● Ptpn2fl/fl + Vehicle, ■ Lck-Cre; Ptpn2fl/fl + Vehicle, ▲ Ptpn2fl/fl + DU-14).