It will be of interest to further investigate by which mechanisms CTL control the rate of association of lytic granules to Rab27a. Such an association suggests that differentiated CTL contain a set of granules prone to rapid secretion and that Rab27a is not the only rate-limiting step of secretion. In agreement, the acquisition of additional molecules such as Munc14-3, via the fusion with endosomal/exocytic vesicles, is required as a final step allowing membrane fusion and subsequent exocytosis. In addition to the regulation of docking, Rab27a may also have additional functions such as the control of intracellular lytic granule motility as recently described. Beyond the apparently homogeneous lytic molecule load of mature CTL lytic granules, Rab27a expression defined two distinct lytic granule subsets in terms of lytic molecule load and size. This indicates that lytic granules coexist in CTL under distinct maturation stages, although such stages cannot be discriminated with the sole analysis of lytic molecule load, probably because of a continuous distribution of this load among individual granules. The presumably more mature Rab27a+ lytic granules were associated with the highest lytic molecule load. The fact that Rab27a+ lytic granules were much larger than the Rab27a2 lytic granules supports the notion that lytic granules fuse to each other and with endosomal structures during maturation, along the steps preceding exocytosis. Very rapidly upon stimulation, the proportion of lytic granules associated to Rab27a increased. In agreement with previous studies, not all lytic granules recruited Rab27a. It is possible that other granules get associated with alternative docking mediators or that the limited Rab27a recruitment is a mechanism for differentiated CTL to hold part of their lytic granules. Our study indeed highlights the fact that CTL do not deplete their lytic granule stock, even under conditions of strong stimulation. This may result from both a limited Rab27a recruitment and from a limited secretion of the lytic granules associated to Rab27a. Sparing a pool of lytic granules is probably key to execute multiple and sequential killing. Additionally, since differentiated CTL appear not to contain conventional lysosomes, the house-keeping degradative functions are most probably ensured by non-secreted lytic granules. In conclusion, our novel approach proves to be a powerful tool for analyzing lytic granule composition during CTL differentiation and activation. This methodology opens new possibilities to better elucidate, in complement with other approaches, the molecular regulation of lytic granule biogenesis and trafficking in both health and pathological settings. Vitiligo is an acquired depigmentary disorder characterized by the appearance of white patches resulting from the loss of functional melanocytes and melanin from the skin and mucous. It affects 0.1–2% of the world population without preference for a specific gender. Several theories about the VE-821 customer reviews pathomechanism of vitiligo have been suggested, including: autoimmune, neural, radical, self destruction and inherent defect theories. However, none of them can explain the pathomechanism of vitiligo perfectly.