Local advantage: skin DCs prime; skin memory T cells protect

Abstract

How the immune system responds to local infection and establish protective immunity within the susceptible tissue remains unclear. Two new studies show local tissue-resident DCs prime CTL responses and memory CTLs remain within the tissue to provide antiviral immunity.

Figure 1

Induction and execution of immune responses against HSV-1 are coordinated by local DCs and memory T cells. (a) Primary infection by HSV-1 is initiated by mechanical scarification of the superficial layer of the epidermis, allowing the virus to enter and replicate locally. HSV-1 infects the innervating ganglion by retrograde transport from the nerve endings in the skin, and establishes latency. Virus introduced via this route is taken up by local skin-resident DCs, which upon migration, present antigens to CD4⁺ T cells. However, cross-priming of CD8⁺ T cells is uniquely carried out by the lymph node-resident CD8α⁺ DCs. (b) Reactivation of the latent virus in the ganglion results in the anterograde migration of infectious virions to the skin and infection of the epithelial cells throughout the dermatome innervated by the ganglion. Following this naturally route of reinfection, the viral antigens are cross-presented to CD8⁺ T cells by CD103⁺ Langerin⁺ DDCs and not the CD8α⁺ DCs. (c) CTL induced by DCs differentiate into three kinds of memory cells, T_CM, T_EM and T_RM. Only the T_RM take up residency in the skin (at the previous site of virus infection) and near the latently infected ganglion. Upon tertiary infection by HSV-1, T_RM provide bulk of the protection even though T_EM can also be recruited to the site from systemic circulation.