The relationship of nyasthenia gravis and apoptosis in human thymus : the anallysis of CAD, DNase and AIF

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 12671322
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Nagoya City University
• Principal Investigator: KIRIYAMA Masanobu Nagoya City University Medical School, Assistant Professor, 医学部, 講師 (30244552)
• Co-Investigator(Kenkyū-buntansha): YAMAKAWA Yosuke Nagoya City University Medical School, Associate Professor, 医学部, 助教授 (40148284) ; FUJII Yoshitaka Nagoya City University Medical School, Professor, 医学部, 教授 (40156831)
• Project Period (FY): 2000 – 2001
• Keywords: caspase / AIF / Negative selection / apoptosis / mitochondria

Research Abstract

Negative selection is a mechanism through which developing thymocytes expressing a TCR with high affinity for self peptide-MHC complexes are eliminated by apoptosis. Isolated human thymocytes were induced to undergo apoptosis by combined use of antii-CD3 and CD28 mAbs. The activation of caspase-3 was detected in thymocytes cultured in the presence of antibodies. Although the activation of caspase-3 was blocked by the caspase inhibitor zVAD.fmk, cell death still occurred with only partial condensation of chromatin and without internucleosomal DNA fragmentation, maintaining other features of apoptosis, such as Δ Ψ_m collapse. We detected expression of AIF in human thymocytes undergoing apoptosis induced by antibodies to CD3 and CD28 in the presence or absence of zVAD.fmk. In the in vitro negative selection model of humam thymocytes, apoptosis can proceed in caspase-dependent and caspase-independent pathways. AIF may be responsible for the latter pathway.