Distinct APC Subtypes Drive Spatially Segregated CD4 and CD8 T-Cell Effector Activity during Skin Infection with HSV-1

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HSV-1 is a widely distributed pathogen causing a life-long latent infection associated with periodic bouts of reactivation and severe clinical complications. Adaptive immune responses encompassing CD4+ and CD8+ T-cell activities are key to both the clearance of infectious virus and the control of latent infection. However, precisely how such T-cell responses are regulated, particularly within acutely infected peripheral tissues, remains poorly understood. Using a mouse model of HSV-1 skin infection, we describe a complex regulation of T-cell responses at the site of acute infection. These responses were subset-specific and anatomically distinct, with CD4+ and CD8+ T-cell activities being directed to distinct anatomical compartments within the skin. While IFN-γ-producing CD4+ T cells were broadly distributed, including skin regions a considerable distance away from infected cells, CD8+ T-cell activity was strictly confined to directly infected epithelial compartments. This unexpected spatial segregation was a direct consequence of the involvement of largely non-overlapping types of antigen-presenting cells in driving CD4+ and CD8+ T-cell effector activity. Our results provide novel insights into the cellular regulation of T-cell immunity within peripheral tissues and have the potential to guide the development of T-cell subset-specific approaches for therapeutic and prophylactic intervention in antimicrobial immunity and autoimmunity.

Vyšlo v časopise: Distinct APC Subtypes Drive Spatially Segregated CD4 and CD8 T-Cell Effector Activity during Skin Infection with HSV-1. PLoS Pathog 10(8): e32767. doi:10.1371/journal.ppat.1004303
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004303

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