Transient gain of effector function by CD8+ T cells undergoing peripheral tolerance to high-dose self-antigen.


Journal Article

Induction of peripheral T cell tolerance is mediated by bone marrow-derived dendritic cells that cross-present self-antigen to self-reactive T cells. The current model for peripheral CD8(+) T cell tolerance is that TCR engagement by self-antigen in the absence of costimulation results in abortive activation without development of effector function. Here we demonstrate in vivo that high-dose self-antigen ("signal 1") can compensate for lack of costimulation ("signal 2"), leading to full activation of and development of effector function by self-reactive T cells. In the setting of low-dose self-antigen, acquisition of effector function by self-reactive T cells is dependent on costimulation via CD40 ligation in vivo. However, gain of effector function in either setting does not prevent eventual tolerance of self-reactive CD8(+) T cells. These results suggest that the mechanisms for peripheral CD8(+) T cell tolerance are more complex than the proposed "signal 1 in the absence of signal 2" hypothesis. Further exploration of these mechanisms will have direct impact on the design of effective immunotherapy for autoimmune diseases, chronic infections and cancers.

Full Text

Cited Authors

  • Huang, X; Yang, Y

Published Date

  • May 2004

Published In

Volume / Issue

  • 34 / 5

Start / End Page

  • 1351 - 1360

PubMed ID

  • 15114668

Pubmed Central ID

  • 15114668

International Standard Serial Number (ISSN)

  • 0014-2980

Digital Object Identifier (DOI)

  • 10.1002/eji.200324734


  • eng

Conference Location

  • Germany