Dapeng Cui

T cell-dependent B-cell responses decline with age, suggesting defective CD4 T-cell function. CD4 memory T cells from individuals older than 65 y displayed increased and sustained transcription of the dual-specific phosphatase 4 (DUSP4) that shortened expression of CD40-ligand (CD40L) and inducible T-cell costimulator (ICOS) (both P < 0.001) and decreased production of IL-4, IL-17A, and IL-21 (all P < 0.001) after in vitro activation. In vivo after influenza vaccination, activated CD4 T cells from elderly individuals had increased DUSP4 transcription (P = 0.002), which inversely correlated with the expression of CD40L (r = 0.65, P = 0.002), ICOS (r = 0.57, P = 0.008), and IL-4 (r = 0.66, P = 0.001). In CD4 KO mice reconstituted with DUSP4 OT-II T cells, DUSP4 had a negative effect on the expansion of antigen-specific B cells (P = 0.003) and the production of ova-specific antibodies (P = 0.03) after immunization. Silencing of DUSP4 in memory CD4 T cells improved CD40L (P < 0.001), IL-4 (P = 0.007), and IL-21 (P = 0.04) expression significantly more in the elderly than young adults. Consequently, the ability of CD4 memory T cells to support B-cell differentiation that was impaired in the elderly (P = 0.004) was restored. Our data suggest that increased DUSP4 expression in activated T cells in the elderly in part accounts for defective adaptive immune responses.

OBJECTIVE: To investigate the inhibiting effects and mechanism of achyranthes bidentata polysaccharide (ABP) and lycium barbarum polysaccharide (LBP) on nonenzyme glycation in D-galactose induced mouse aging model. METHODS: Serum AGE levels were determined by AGE-ELISA, MTT method was used to determine lymphocyte proliferation, IL-2 activity was determined by a bioassay method. Spontaneous motor activity was used to detect mouse's neuromuscular movement, latency of step-through method was used to examine learning and memory abilities of mouse, colormetric assay was used to determine hydroxyproline concentration in mouse skin, pyrogallol autoxidation method was used to determine superoxide dismutase (SOD) activity of erythrocytes. RESULTS: Decreased levels of serum AGE, hydroxyproline concentration in mouse skin and spontaneous motor activity in D-galactose mouse aging model were detected after treated with ABP or LBP, while lymphocyte proliferation and IL-2 activity, learning and memory abilities, SOD activity of erythrocytes, were enhanced. CONCLUSIONS: ABP and LBP could inhibit nonenzyme glycation in D-galactose induced mouse aging model in vivo and ABP has a better inhibiting effect than LBP.

Killer immunoglobulin-like receptors (KIRs) are a family of regulatory cell-surface molecules expressed on natural killer (NK) cells and memory T-cell subsets. Their ability to prevent the formation of an activation platform and to inhibit NK cell activation is the basis of the missing self model of NK cell function. The benefits of KIR expression for T-cell biology are unclear. We studied how KIR2DL2 regulates T-cell function. Engagement of KIR2DL2 by the ligand human leukocyte antigen (HLA)-Cw3 did not affect conjugate formation between CD4(+)KIR2DL2(+) T cells and superantigen-pulsed target cells or the development of mature immune synapses with lipid rafts. KIR2DL2 and the corresponding HLA-C ligand were initially recruited to the peripheral supramolecular activation cluster (pSMAC). Consequently, KIR2DL2 engagement did not inhibit the phosphorylation of early signaling proteins and T-cell-receptor (TCR)-mediated cytotoxicity or granule exocytosis. After 15-30 minutes, KIR2DL2 moved to the central supramolecular activation cluster (cSMAC), colocalizing with CD3. TCR synapses dissociated, and phosphorylated phospholipase C (PLC)-gamma1, Vav1, and extracellular signal-regulated kinase 1/2 (ERK1/2) were reduced 90 minutes after stimulation. Gene array studies documented that the inhibition of late signaling events by KIR2DL2 affected transcriptional gene activation. We propose that KIRs on memory T cells operate to uncouple effector functions by modifying the transcriptional profile while leaving granule exocytosis unabated.