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Journal Article
Cross-priming in health and disease
2010
Overview
Key Points
Cross-presentation allows dendritic cells (DCs) to activate CD8
+
cytotoxic T lymphocytes (CTLs) for immune defence against viruses that do not infect DCs and tumours that originate from non-DCs.
Immunogenic cross-presentation (cross-priming) requires that DCs are licensed by T helper (T
H
) cells or natural killer T (NKT) cells, which renders them competent to programme CTLs for survival, effector function and memory cell generation.
Licensing T
H
or NKT cells cause DCs to produce discrete chemokines that recruit naive CTLs into lymphatic tissues for cross-priming. Also, DC–T
H
cell interaction in non-lymphatic tissues results in chemokine production that recruits cross-primed CTLs for cytotoxic effector functions, which promote antiviral defence and immune-mediated disease.
Cross-priming allows for the expansion of CTLs and the induction of antiviral immunity even in the presence of viral immune escape from MHC class I presentation in infected cells
Cross-presentation of autoantigens causes deletion of autoreactive CTLs that have escaped central tolerance; failure of such cross-tolerance is thought to contribute to the pathogenesis of autoimmune diseases, such as type 1 diabetes, multiple sclerosis and psoriasis.
Many tumour antigens are effectively cross-presented but this rarely results in effective cross-priming. Vaccination strategies that combine tumour antigens with adjuvants that mature DCs and increase cross-presentation and chemokine production may overcome this problem when combined with suitable chemotherapies that do not compromise antitumour immunity.
The activation of cytotoxic T lymphocytes by cross-presented antigen (known as cross-priming) is necessary for immunity against certain viruses, bacteria and most tumours. Here, the underlying cellular and molecular mechanisms of cross-priming are described, providing insight into some central questions on the basic mechanisms of cross-priming, and its physiological and therapeutic importance are discussed.
Cross-priming is an important mechanism to activate cytotoxic T lymphocytes (CTLs) for immune defence against viruses and tumours. Although it was discovered more than 25 years ago, we have only recently gained insight into the underlying cellular and molecular mechanisms, and we are just beginning to understand its physiological importance in health and disease. Here we summarize current concepts on the cross-talk between the immune cells involved in CTL cross-priming and on its role in antimicrobial and antitumour defence, as well as in immune-mediated diseases.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
