Developmentally regulated expression of the PD-1 protein on the surface of double-negative (CD4-CD8-) thymocytes.
PD-1, a member of the Ig superfamily, was previously isolated from an apoptosis-induced T cell hybridoma 2B4.11 by subtractive hybridization. Expresson of the PD-1 mRNA is restricted to thymus in adult mice. Using an anti-PD-1 mAb (J43), we examined expression of the PD-1 protein during differentiation of thymocytes in normal adult, fetal and RAG-2(-/-) mice with or without anti-CD3 mAb stimulation. While PD-1 was expressed only on 3-5% of total normal thymocytes, approximately 34% of the CD4(-)CD8(-) double-negative (DN) fraction are PD-1(+) cells with two distinct expression levels (low and high). PD-1(high) thymocytes belonged to TCR gammadelta lineage cells. In the DN compartment of the TCR alphabeta lineage, PD-1 expression started at the low level from the CD44(+)CD25(+) stage and the majority of thymocytes expressed PD-1 at the CD44(-)CD25(-) stage in which the thymocytes express TCR beta chains. The anti-CD3epsilon antibody administration augmented the PD-1 expression as well as the differentiation of the CD44(-)CD25(+) DN cells into the CD44(-)CD25(-) DN stage, not only in normal mice but also in RAG-2-deficient mice. The fraction of the PD-1(low) cells in the CD4(+)CD8(+) double-positive (DP) compartment was very small (<5%) but increased by stimulation with the anti-CD3 antibody, although the total number of DP cells was drastically reduced. The results show that PD-1 expression is specifically induced at the stages preceding clonal selection.
Nishimura
H
H
Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Japan.
Agata
Y
Y
Kawasaki
A
A
Sato
M
M
Imamura
S
S
Minato
N
N
Yagita
H
H
Nakano
T
T
Honjo
T
T
D000375:Aging / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000954:Antigens, Surface / Q000096:biosynthesis*; D051017:Apoptosis Regulatory Proteins; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000502:physiology*; D016827:CD8 Antigens / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D004268:DNA-Binding Proteins; D005260:Female; D018960:Hyaluronan Receptors / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D061026:Programmed Cell Death 1 Receptor; D011506:Proteins / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000145:classification* / Q000166:cytology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D004268:DNA-Binding Proteins; D018960:Hyaluronan Receptors; D009363:Neoplasm Proteins; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D011506:Proteins; C499308:Rag2 protein, mouse; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015375:Receptors, Interleukin-2; C064655:V(D)J recombination activating protein 2