The Enhancing IL-2R alpha mRNA Expression induces A Marked T Cel Proliferation with Interleukin-2 and Anti-CD3 mAb

Kim, Hwa Jung; Jo, Eun Kyeong; Park, Jeong Kyu; Kim, Jong Kun

Abstract

Culture of human peripheral T lymphocytes with irnmobilized anti-CD3 rnAb plus IL-2 resulted in a marked proliferation and the enhancing IL-2Ra mRNA expression. The process of the T cell activation involves a series of biochemical events which ultimately lead to the proliferation and IL-2Ra mRNA expression. Although the above results have been observed, the celluar signal mechanisms between the proliferative response and the IL-2Ra mRNA expression through T cell receptor and IL-2 receptor remains unresolved. In the present study, We have used genistein (the selective PTK inhibitor) or chronic PMA treatment (depletion of intracelluar PKC activity), to investigate the role of PTK or PKC both in a synergistic proliferation and in the enhancing IL-2Ra mRNA expression by IL-2/anti-CD3. Genistein (30 ug/ml) completely blocked IL-2 induced T cell proliferation, and inhibited anti-CD3 induced T cell proliferation (93.4%). But genistein downregulated the IL-2Ra mRNA expression by IL-2, anti-CD3 and IL-2/anti-CD3. The chronic PMA treatment failed to inhibit the proliferation and the IL-2R#u mRNA expression by IL-2 alone. But PKC depleted T cells stimulated with anti-CD3 mAb showed the decrease of the proliferation (68.6%) and IL-2Ra mRNA expression. In activated with IL-2/anti- CD3, the proliferative response showed a half of reduction, but the IL-2Ra mRNA expression were not regulated. These results demonstrate that proliferative response to IL-2 appears to be dependent on PTKs activity and independent of PKC involvement, but the IL-2Ra mRNA expression may be required another signals. PTKs and PKC activity may be important in TCR/CD3 signaling. But IL-2/anti-CD3 are coupled up different signal transduction pathways responsible for the synergistic T cell proliferation and the enhancing IL-2Ru mRNA expression.