Evidence of synergy between Thy-1 and CD3/TCR complex in signal delivery to murine thymocytes for cell death

Izumi Nakashima, Yue Hua Zhang, S. M.Jamshedur Rahman, Tomoaki Yoshida, Ken Ichi Isobe, Lin Na Ding, Takashi Iwamoto, Michinari Hamaguchi, Hiroh Ikezawa, Ryo Taguchi

Research output: Contribution to journalArticlepeer-review

74 Citations (Scopus)


The potential role of Thy-1 in CD3/TCR complex-mediated signal delivery to murine thymocytes was studied. Ag-mimicking cross-linked anti-CD3 mAb stimulated suspension of thymocytes from adult (6 to 8 wk old) mice for a brisk free cytoplasmic calcium ion ([Ca2+]i) rise, low level of inositol phosphate production, and marginal increase in tyrosine-specific phosphorylation of 110/120-kDa and 40-kDa cellular proteins. Weak but sustained [Ca2+]i rise, low inositol phosphate production, and weak protein tyrosine phosphorylation were also induced by the cross-linked anti-Thy-1 mAb that mimicked the putative natural ligand. The signal delivered via either of these two pathways was however insufficient for definitively promoting cell death and DNA fragmentation in the adult thymocytes. Here we demonstrated that anti-Thy-1 mAb synergized with anti-CD3 mAb for inducing a long-lasting prominent [Ca2+]i rise, definite inositol 1,4,5-triphosphate and inositol 1,3,4,5-tetrakiphosphate production, and extensive tyrosine-specific phosphorylation of 110/ 120-, 92-, 75-, and 40-kDa proteins, which resulted in marked promotion of cell death and DNA fragmentation in the adult thymocytes. This unique anti-Thy-1 antibody activity was confirmed to be directed to glycosylphosphatidylinositol-anchored Thy-1, and was distinguished from the known anti-L3T4 activity that augmented the CD3-mediated signal transduction in a different manner. The synergistic actions of anti-CD3 and anti-Thy-1 mAb obligatorily required the cross-linking of the two mAb together. The anti-CD3 and anti-Thy-1 mAb cross-linked together acted on immature thymocytes from newborn (<24 h after birth) mice for rather more extensive promotion of protein tyrosine phosphorylation and cell death. In addition, they affected peripheral T lymphocytes for accelerating protein tyrosine phosphorylation but not cell death. These results suggest a novel function of glycosylphosphatidylinositol-anchored Thy-1 as a possible unique intrathymic intensifier of the CD3/TCR complexdelivered signal for negative thymocyte selection.

Original languageEnglish
Pages (from-to)1153-1162
Number of pages10
JournalJournal of Immunology
Issue number4
Publication statusPublished - 15-08-1991

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'Evidence of synergy between Thy-1 and CD3/TCR complex in signal delivery to murine thymocytes for cell death'. Together they form a unique fingerprint.

Cite this