T-cell tolerance or function is determined by combinatorial costimulatory signals. EMBO J 2006 Jun 07;25(11):2623-33
Date
05/26/2006Pubmed ID
16724117Pubmed Central ID
PMC1478197DOI
10.1038/sj.emboj.7601146Scopus ID
2-s2.0-33745736420 (requires institutional sign-in at Scopus site) 201 CitationsAbstract
Activated in immune responses, T lymphocytes differentiate into effector cells with potent immune function. CD28 is the most prominent costimulatory receptor for T-cell activation. However, absence of CD28 costimulation did not completely impair effector function of CD4 or CD8 T cells. Moreover, increasing number of costimulatory molecules are recently found on antigen-presenting cells to regulate T-cell activation. To understand the molecular mechanisms that determine T-cell function or tolerance, we have collectively examined the roles of positive and negative costimulatory molecules. Antigen-specific naïve CD4 and CD8 T cells, only when activated in the absence of both CD28 and ICOS pathways, were completely impaired in effector function. These tolerant T cells not only were anergic with profound defects in TcR signal transduction but also completely lacked expression of effector-specific transcription factors. T-cell tolerance induction in this system requires the action by negative costimulatory molecules; T-cell proliferation and function was partially restored by inhibiting PD-1, B7-H3 or B7S1. This work demonstrates that T-cell function or tolerance is controlled by costimulatory signals.
Author List
Nurieva R, Thomas S, Nguyen T, Martin-Orozco N, Wang Y, Kaja MK, Yu XZ, Dong CAuthor
Xue-Zhong Yu MD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntigens, Differentiation, T-Lymphocyte
B7-1 Antigen
CD28 Antigens
Cells, Cultured
Immune Tolerance
Inducible T-Cell Co-Stimulator Protein
Interleukin-2
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, Antigen, T-Cell
Signal Transduction
T-Lymphocyte Subsets
T-Lymphocytes
Transcription, Genetic
