This study investigates the regulation of dendritic cell (DC) numbers and maturation in vivo following lipopolysaccharide (LPS) administration. DCs are known to have the capacity to sensitize T cells upon first encountering antigens, a process termed "maturation." The authors found that before LPS treatment, many DCs were located in the marginal zone between the red and white pulp of the spleen, lacking the M342 and DEC-205 markers but effectively processing soluble proteins. After 6 hours of LPS treatment, DCs with the M342 and DEC-205 markers increased in number in the T cell areas, showing reduced protein processing capacity but enhanced B7 costimulator and T cell stimulatory capacity. However, 48 hours after LPS, the number of DCs in the spleen significantly decreased, correlating with impaired T cell activation in vitro and in vivo. These findings suggest that LPS induces DC migration from the marginal zone to the T cell areas, leading to their maturation and subsequent loss, which may be part of a negative feedback mechanism to control inflammatory responses. The study also highlights the role of microbial products in regulating DC function and the potential evolutionary advantage of bacteria in retaining immunogenic components that can reduce host resistance.This study investigates the regulation of dendritic cell (DC) numbers and maturation in vivo following lipopolysaccharide (LPS) administration. DCs are known to have the capacity to sensitize T cells upon first encountering antigens, a process termed "maturation." The authors found that before LPS treatment, many DCs were located in the marginal zone between the red and white pulp of the spleen, lacking the M342 and DEC-205 markers but effectively processing soluble proteins. After 6 hours of LPS treatment, DCs with the M342 and DEC-205 markers increased in number in the T cell areas, showing reduced protein processing capacity but enhanced B7 costimulator and T cell stimulatory capacity. However, 48 hours after LPS, the number of DCs in the spleen significantly decreased, correlating with impaired T cell activation in vitro and in vivo. These findings suggest that LPS induces DC migration from the marginal zone to the T cell areas, leading to their maturation and subsequent loss, which may be part of a negative feedback mechanism to control inflammatory responses. The study also highlights the role of microbial products in regulating DC function and the potential evolutionary advantage of bacteria in retaining immunogenic components that can reduce host resistance.