Avidity maturation of memory CD8 T cells is limited by self-antigen expression
Authors
Turner, Michael J.Jellison, Evan Robert
Lingenheld, Elizabeth G.
Puddington, Lynn
Lefrancois, Leo
Document Type
Journal ArticlePublication Date
2008-07-16Keywords
Animals; Autoantigens; Autoimmunity; CD8-Positive T-Lymphocytes; Cell Differentiation; Cross Reactions; Female; Immune Tolerance; *Immunologic Memory; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Ovalbumin; Peptide Fragments; Self Tolerance; Transcription Factors; Vesicular stomatitis Indiana virusLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Immune tolerance to self-antigens is a complex process that utilizes multiple mechanisms working in concert to maintain homeostasis and prevent autoimmunity. We developed a system that revealed a population of self-specific CD8 T cells within the endogenous T cell repertoire. Immunization of ovalbumin (OVA)-expressing transgenic mice with recombinant viruses expressing OVA-peptide variants induced self-reactive T cells in vivo that matured into memory T cells able to respond to secondary infection. However, whereas the avidity of memory cells in normal mice increased dramatically with repeated immunizations, avidity maturation was limited for self-specific CD8 T cells. Despite decreased avidity, such memory cells afforded protection against infection, but did not induce overt autoimmunity. Further, up-regulation of self-antigen expression in dendritic cells using an inducible system promoted programmed death-1 expression, but not clonal expansion of preexisting memory cells. Thus, the self-reactive T cell repertoire is controlled by overlapping mechanisms influenced by antigen dose.Source
J Exp Med. 2008 Aug 4;205(8):1859-68. Epub 2008 Jul 14. Link to article on publisher's siteDOI
10.1084/jem.20072390Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32989PubMed ID
18625745; 18625745Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1084/jem.20072390