In multiple sclerosis (MS4) B cell depleting therapy using monoclonal anti-CD20 antibodies, including rituximab (RTX) and ocrelizumab (OCR), effectively reduces disease activity. Based on indirect evidence, it is generally believed that elimination of the antigen presenting capabilities and antigen non-specific immune functions of B cells underlie the therapeutic efficacy. However, a small subset of T lymphocytes (T cells) was shown to also express CD20, but controversy prevails surrounding the true existence of this T cell subpopulation. Using single-cell imaging flow cytometry and expression profiling of sorted lymphocyte subsets, we unequivocally demonstrate the existence of CD3+CD20dim T cells. We show that in MS patients increased levels of CD3+CD20dim T cells are effectively depleted by RTX. The pathological relevance of this T cell subset in MS remains to be determined. However, given their potential pro-inflammatory functionality, depletion of CD20-expressing T cells may also contribute to the therapeutic effect of RTX and other monoclonal antibodies targeting CD20.

Brief exposure to real-world levels of SHS leads to sustained vascular injury characterized by mobilization of dysfunctional EPCs with blocked nitric oxide production. Our results suggest that SHS not only affects the vascular endothelium, but also the function of EPCs.

Sustained improvements in endothelial dysfunction by regular dietary intake of flavanols are associated with mobilization of functional CACs. (Effect of Cocoa Flavanols on Vascular Function in Optimally Treated Coronary Artery Disease Patients: Interaction Between Endothelial Progenitor Cells, Reactivity of Micro- and Macrocirculation; NCT00553774).

Objective-Circulating angiogenic cells (CACs), also termed endothelial progenitor cells, play an integral role in vascular repair and are functionally impaired in coronary artery disease (CAD). The role of nitric oxide (NO) in CAC function is poorly understood. We hypothesized that CAC migration toward angiogenic signals is modulated by both NO synthase (NOS) expression and functional response to NO. Methods and Results-Similar to endothelial cells, CAC chemotaxis to vascular endothelial growth factor (VEGF) was blocked by inhibition of NOS, phosphatidylinositol 3-kinase, or guanylyl cyclase or by treatment with an NO scavenger. Addition of an NO donor (S-nitroso-N-acetylpenicillamine) and the NOS substrate L-arginine increased random cell migration (chemokinesis) and enhanced VEGF-dependent chemotaxis. Healthy CACs expressed endothelial NOS, but endothelial NOS was not detected in CAD patient CACs. Both chemokinesis and chemotaxis to VEGF of patient CACs were decreased compared with healthy CACs but were restored to healthy values by S-nitroso-N-acetylpenicillamine. In parallel, CAD patients exhibited lower flow-mediated vasodilation and plasma NO source nitrite than young, healthy subjects, indicating endothelial dysfunction with reduced NO bioavailability. Conclusion-NOS activity is required for CAC chemotaxis. In CAD patients, impairment of NOS expression and NO bioavailability, rather than response to NO, may contribute to dysfunction of CACs and limit their regenerative capacity. Physiologically, many integral functions of the vascular endothelium are modulated by endothelial nitric oxide synthase (eNOS)-derived NO, including the inhibition of platelet and leukocyte adhesion, smooth muscle relaxation, and proliferation. Newer literature shows that NO not only acts in paracrine manner but may also exert systemic effects via reversible formation of more stable storage forms, including nitrite and nitoso-adducts. The disruption of this pathway in endothelial cells is associated with chronic vascular disease. 2 Risk factors appear to selectively damage the vascular endothelium, leading to a dysfunctional, maladaptive endothelial phenotype. 3,4 Studies suggest that eNOS activity and expression as well as circulating NO storage forms in blood are progressively decreased with cardiovascular risk factors including aging, hypertension, hypercholesterolemia, diabetes, and smoking and cigarette smoke exposure. 2,[5][6][7] Over time, chronic endothelial dysfunction leads to intimal hyperplasia and enhanced plaque formation in predisposed areas of the vascular tree. Notably, the functional capacity of the vascular endothelium not only depends on the degree of damage but also on the presence and status of repair systems, including circulating angiogenic cells (CACs). 8 Vascular repair involves not only local migration and proliferation of mature endothelial cells but also angiogenic cells that circulate in blood and the recruitment of the latter cells to sites of injury. Literature from the last 10 years suggests tha...