Regulation of dendritic cell function by microbial stimuli.

Dendritic cells (DC) initiate T cell responses and produce cytokines and other molecules that can regulate the class adaptive immunity. It is increasingly clear that DC in vivo are in a "resting" state and require exogenous signals to transit into an "effector" state in which they can prime T cells. Much of this DC activation process appears to be regulated by infection. Exposure of murine DC to certain pathogens or their products triggers DC migration to T cell areas of secondary lymphoid tissues, improves MHC presentation and increases DC co-stimulatory potential. Pathogen recognition can also initiate cytokine production and/or condition DC to produce cytokines in response to subsequent T cell feedback signals delivered via CD40 and similar receptors. Recognition of pathogens by DC is largely dependent on Toll-like receptors (TLRs). Interestingly, mouse splenic CD8alpha+ and CDalpha-CD4- DC have the ability to produce either IL-12 p70 or IL-10 depending on the nature of the pathogen encountered. In contrast, CD4+ DC seem incapable of producing IL-12 p70. Thus, the nature of the pathogen can dictate the type of cytokine that is made by some DC subsets, allowing them to prime distinct types of immune responses. Overall, DC display significant plasticity in their ability to respond to infection and direct adaptive immunity.

Lactate dehydrogenase-elevating virus (LDV): lifelong coexistence of virus and LDV-specific immunity.

Viruses have developed various strategies to coexist with vertebrate hosts. Lactate dehydrogenase-elevating virus (LDV) is a highly cytopathic virus exhibiting an extraordinary rate of replication; LDV nevertheless establishes a persistent infection without harming the host. The cytotoxic and helper T cell responses to LDV were monitored in mice with different genetic backgrounds. LDV-specific cytotoxic and helper T cells were found in all strains tested. These responses persisted for at least up to 250 days despite high levels of LDV in the blood. Thus, the cytopathic LDV induces and maintains an inefficient immune response that is not exhausted. LDV infection in mice reveals a special type of host-virus equilibrium where LDV quickly establishes persistence despite continuously induced LDV-specific helper and cytotoxic T cell responses, which apparently are too slow to control the highly cytopathic and extremely fast replicating virus.