To be,or not to be immunocompetent

Several data support the view that impairment of the inflammatory-immune response is a hallmark of severe sepsis and the level and time of recovery to immunocompetence has a major impact on the clinical outcome of ICU patients. Recent studies demonstrate that improvement of anti-tumour immune response by targeting negative regulatory molecules, such as CD25, chronic T-lymphocyte activation antigen 4, and programmed death-1 receptor (PD-1)/PD-1 L, offers a novel opportunity to prevent or even reverse progression of tumour growth in experimental models and patients. Likewise, severe sepsis is associated with enhanced expression of those negative regulatory molecules, suggesting a novel approach to reverse immunoparalysis in sepsis. Consequently, targeting negative molecules in sepsis can reverse immunoparalysis and improve survival in experimental sepsis, as shown by Chang and colleagues in a recent issue of Critical Care. This opens new opportunities to overcome overwhelming downregulation of the adaptive immune response to prevent and/or improve recovery from sepsis.     

To be or not to be B7

The activation of lymphocytes and development of adaptive immune responses is initiated by the engagement of TCRs by antigenic peptide-MHC complexes and shaped at the clonal level by both positive and negative costimulatory signals. The B7 family members are involved at several stages in this process. In this issue of the JCI, Vogt et al. show that the B7 family-related protein V-set and Ig domain-containing 4 (VSIG4) can act as an inhibitor of T cell activation (see the related article beginning on page 2817). Intriguingly, the same molecule was recently independently identified as a complement receptor of the Ig superfamily (CRIg) and was convincingly demonstrated to be a receptor for complement component 3 fragments. These findings raise interesting questions regarding the physiological roles and mechanisms of action of this molecule. Identification of dual functions of this molecule provides an additional level of complexity in T cell costimulation.     

To be

In homecare, skill, education, and experience are vital to success. When the ability to know when to be something instead of do something is learned, the true art is born.