Rabbit Anti-Human CD40 (Phospho-Thr254) polyclonal antibody

CD40-activated CD40L reverse signaling is a major physiological regulator of neural process growth from many kinds of developing neurons. Here we have investigated whether CD40L-reverse signaling also influences dendrite spine number and morphology in striatal medium spiny neurons (MSNs). Golgi preparations revealed no differences in the spine density, but because the dendrite arbors of MSNs were larger and branched in Cd40(-/-) mice, the total number of spines was greater in Cd40(-/-) mice. We also detected more mature spines compared with wild-type littermates. Western blot revealed that MSN cultures from Cd40(-/-) mice had significantly less PSD-95 and there were changes in RhoA/B/C and Cdc42. Immunocytochemistry revealed that PSD-95 was clustered in spines in Cd40(-/-) neurons compared with more diffuse labeling in Cd40(+/+) neurons. Activation of CD40L-reverse signaling with CD40-Fc prevented the changes observed in Cd40(-/-) cultures. Our findings suggest that CD40L-reverse signaling influences dendrite spine morphology and related protein expression and distribution.

T-cell-stimulating cytokines have shown promise as monotherapies or in combination with other therapeutic modalities for immunotherapy of cancer. However, their efficacy is limited due to their short half-life, pleiotropic roles, and induction of severe toxicity even at therapeutic doses. To overcome these major therapeutic barriers, cytokine-based products are being further developed to improve their therapeutic index. These approaches include manipulating their activity to preferentially bind to effector immune cells rather than immune-suppressive cells, prolonging their half-life in vivo and modifying them to target tumors. This review focuses on IL-2, IL-15, and IL-10, which have potent effects on immune cells that mediate effective antitumor responses. We will summarize the recent progress of these cytokines in both preclinical studies and selective clinical applications and will discuss our perspectives on the development of new strategies to potentiate cytokine-based immunotherapy.