Interleukin-2와 Anti-CD3 단클론항체에 의한 T세포 증식 상승효과에 대한 Protein tyrosine kinase와 Protein kinase C의 역할

다국어 초록 (Multilingual Abstract)

Culture of human peripheral T lymphocytes with immobilized anti-CD3 mAb plus IL-2 resulted in a marked proliferation. Although a synergistic response of immobilized anti-CD3 and interleukin-2 (IL-2) has been reported, the mechanism of the celluar signal transduction through T cell receptor(TCR) and IL-2 receptor(IL-2R) remains unresolved.
The process of the T ce11 activation involves a series of biochemical events which ultimately leads to lymphocyte proliferation.
The CD3/TCR is known to activate two signal transduction pathways. The first one is the activation of a protein kinase C(PKC) and a rise in intracelluar calcium levels The second pathway operates through protein tyrosine kinases(PTKs). Stimulation of the IL-2R induces an increase tyrosine phosphorylation of several celluar proteins by PTKs.
In the present study, I have used the selective PTK inhibitor(genistein) or chronic PMA treatment(depletion of intracelluar PKC activity), to investigate the role of PTK or PKC in synergistic proliferation signals delivered by TCR and IL-2R. Genistein(30pg/ml) completely blocked IL-2 induced T cell proliferation, and inhibited anti-CD3 mAb or IL-2/anti-CD3 mAb induced T cell proliferation(93%, 94% respectively). The chronic PMA treatment, which depletes intracelluar PKC activity, failed to inhibit the proliferative response of T cell stimulated with IL-2 alone. But the chronic PMA treatment inhibit the proliferative response of T cell stimulated by anti-CD3 or anti-CD3 mAb plus IL-2(68.6%, 49.1% repectively) These results demonstrate that proliferation of T cells triggered via IL-2R appears to be dependent on PTKs activity and independent of PKC invovement. PTKs and PKC activity may be important in TCR/CD3 signaling. But the TCR/CD3 and IL-2R are coupled to different signal transduction pathways responsible for the synergistic T cell proliferation.

목차 (Table of Contents)

• 목차
• I. 서론 = 1
• II. 실험재료 및 방법 = 3
• III. 결과 = 6
• IV. 고찰 = 12
• V. 결론 = 15
• 참고문헌 = 17
• Abstract = 20