(Journal Article): Facilitation of beta selection and modification of positive selection in the thymus of PD-1-deficient mice.
 
Nishimura H, Honjo T, Minato N (Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.)
 
IN: J Exp Med 2000; 191(5):891-898
Impact Factor(s) of J Exp Med: 14.588 (2004), 15.302 (2003), 15.34 (2001)

Fulltext:    HTML  PDF

ABSTRACT: PD-1 is an immunoglobulin superfamily member bearing an immunoreceptor tyrosine-based inhibitory motif, and disruption of the PD-1 gene results in the development of lupus-like autoimmune diseases. In this study, we examined effects of the PD-1 deficiency on the thymocyte differentiation at the clonal level using T cell receptor (TCR)-beta (Vbeta8) and TCR-alpha/beta (H-Y and 2C) transgenic mice. In these TCR transgenic lines, PD-1 expression in the thymus was variably augmented, but as in the normal mice, confined largely to the CD4(-)CD8(-) thymocytes. The transgenic mice crossed with PD-1(-/)- mice in the neutral genetic backgrounds exhibited selective increase in the CD4(+)CD8(+) (DP) population with little effect on other thymocytes subsets. Similarly, the absence of PD-1 facilitated expansion of DP thymocytes in recombination activating gene (RAG)-2(-/)- mice by anti-CD3epsilon antibody injection. On the other hand, H-Y or 2C transgenic PD-1(-/)- mice with the positively selecting background showed significantly reduced efficiency for the generation of CD8(+) single positive cells bearing the transgenic TCR-alpha/beta in spite of the increased DP population. These results collectively indicate that PD-1 negatively regulates the beta selection and modulates the positive selection, and suggest that PD-1 deficiency may lead to the significant alteration of mature T cell repertoire.

TYPE OF PUBLICATION: Original article

Articles citing this article:

• Yadav D, Sarvetnik N. Costimulation and Pancreatic Autoimmunity: The PD-1/PD-L Conundrum. Rev Diabetic Stud 2006. 3: 6-10.
  » Diabetes OD » Development and Function of Pa... » Immune System » Activation and Inhibition » Costimulation » Programmed Death » Journal Article