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

PLoS Pathogens

Bethany L. Macleod¹  William R. Heath¹  Scott N. Mueller¹  Jyh Liang Hor¹  Sammy Bedoui¹  Thomas Gebhardt¹  Andrew G. Brooks¹  Tiffany A. Russell²  Natasha A. Hollett²  David C. Tscharke² 

[1] Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia;Division of Biomedical Science and Biochemistry, Research School of Biology, The Australian National University, Canberra, Australian Capital Territory, Australia

关键词: Skin infections;    T cells;    Cytotoxic T cells;    Antigen-presenting cells;    Epidermis;    Inflammation;    Keratinocytes;    Antibodies;   

DOI  :  10.1371/journal.ppat.1004303

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Efficient infection control requires potent T-cell responses at sites of pathogen replication. However, the regulation of T-cell effector function in situ remains poorly understood. Here, we show key differences in the regulation of effector activity between CD4+ and CD8+ T-cells during skin infection with HSV-1. IFN-γ-producing CD4+ T cells disseminated widely throughout the skin and draining lymph nodes (LN), clearly exceeding the epithelial distribution of infectious virus. By contrast, IFN-γ-producing CD8+ T cells were only found within the infected epidermal layer of the skin and associated hair follicles. Mechanistically, while various subsets of lymphoid- and skin-derived dendritic cells (DC) elicited IFN-γ production by CD4+ T cells, CD8+ T cells responded exclusively to infected epidermal cells directly presenting viral antigen. Notably, uninfected cross-presenting DCs from both skin and LNs failed to trigger IFN-γ production by CD8+ T-cells. Thus, we describe a previously unappreciated complexity in the regulation of CD4+ and CD8+ T-cell effector activity that is subset-specific, microanatomically distinct and involves largely non-overlapping types of antigen-presenting cells (APC).

【 授权许可】

CC BY