Clonal exhaustion as a result of immune deviation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2003-05

AUTHORS

Can Keşmir, Rob J. De Boer

ABSTRACT

An overwhelming virus infection that spreads within a few days throughout the host can cause deletion of the specific cytotoxic T lymphocytes (CTL). This phenomenon is known as ‘clonal exhaustion’. Current explanations for this phenomenon are ‘clonal’, and consider either the terminal differentiation of the virus-specific CTL to an effector phenotype, or the lack of help and antigen presentation for a specific CTL clone. The virus remains controlled by some other form of immunity in the exhausted state. Candidates are innate immunity (especially NK cells andmacrophages) and a T helper type 2 based immune response. Surprisingly, the role of this other form of immunity in causing exhaustion has been ignored so far. Developing a mathematical model, we here investigate the possibility that this inter-clonal immunity is responsible for exhaustion by down regulating the CTL response. The model is based on previously published exhaustion data for Lymphocytic choriomeningitis virus as an in vivo model. We demonstrate that several complicated experiments on clonal exhaustion are consistentwith inter-clonal regulation. By interpreting the available data with a mathematical model, we compare this novel mechanism with the mechanisms suggested previously. More... »

PAGES

359-374

Identifiers

URI

http://scigraph.springernature.com/pub.10.1016/s0092-8240(03)00009-0

DOI

http://dx.doi.org/10.1016/s0092-8240(03)00009-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1033640449

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12749529


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