Antiviral CD8+ T cell effector activities in situ are regulated by target cell type (2024)

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Gabriele Neumann, Takeshi Noda, Yoshihiro Kawaoka (2009)

Influenza viruses cause annual epidemics and occasional pandemics that have claimed the lives of millions. The emergence of new strains will continue to pose challenges to public health and the scientific communities. A prime example is the recent emergence of swine-origin H1N1 viruses that have transmitted to and spread among humans, resulting in outbreaks internationally. Efforts to control these outbreaks and real-time monitoring of the evolution of this virus should provide us with invaluable information to direct infectious disease control programmes and to improve understanding of the factors that determine viral pathogenicity and/or transmissibility.

M Albert, B Sauter, N Bhardwaj (1998)

CD8+ cytotoxic T lymphocytes (CTLs) mediate resistance to infectious agents and tumours. Classically, CTLs recognize antigens that are localized in the cytoplasm of target cells, processed and presented as peptide complexes with class I molecules of the major histocompatibility complex (MHC). However, there is evidence for an exogenous pathway whereby antigens that are not expected to gain access to the cytoplasm are presented on MHC class I molecules. The most dramatic example is the in vivo phenomenon of cross-priming: antigens from donor cells are acquired by bone-marrow-derived host antigen-presenting cells (APCs) and presented on MHC class I molecules. Two unanswered questions concern the identity of this bone-marrow-derived cell and how such antigens are acquired. Here we show that human dendritic cells, but not macrophages, efficiently present antigen derived from apoptotic cells, stimulating class I-restricted CD8+ CTLs. Our findings suggest a mechanism by which potent APCs acquire antigens from tumours, transplants, infected cells, or even self-tissue, for stimulation or tolerization of CTLs.

Jie Sun, Rajat Madan, Christopher Karp … (2009)

Activated antigen-specific T cells produce a variety of effector molecules for clearing infection, but also contribute significantly to inflammation and tissue injury. Here we report an anti-inflammatory property of anti-viral CD8+ and CD4+ effector T cells (Te) in the infected periphery during acute virus infection. We find that, during acute influenza infection, IL-10 is produced in the infected lungs at high levels -- exclusively by infiltrating virus-specific Te, with CD8+ Te contributing a larger fraction of the IL-10 produced. These Te in the periphery simultaneously produce IL-10 and proinflammatory cytokines, and express lineage markers characteristic of conventional Th/c1 cells. Importantly, blocking the action of the Te-derived IL-10 results in enhanced pulmonary inflammation and lethal injury. Our results demonstrate that anti-viral Te exert regulatory functions -- that is, fine-tune the extent of lung inflammation and injury associated with influenza infection by the production of an anti-inflammatory cytokine. The potential implications of these findings for infection with highly pathogenic influenza viruses are discussed.