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Epidermal Growth Factor가 림프구 기능 조절 작용에 미치는 영향에 관한 실험적 연구
우건희,신형식 원광대학교 치의학연구소 1991 圓光齒醫學 Vol.1 No.2
Epidermal growth factor(EGF), single-chain polypeptide(MW 6045) has been known as a potent extracellular regulator of biological responses in a wide variety of cell types. However, little has been reported about the role of EGF in the regulation of lymphocyte-function. Moreover, the mechanisms of EGF-action on immune system has not yet been elucidated. The purpose of this study was to investigate on the in vitro effect of EGF on proliferation of T and B lymphocytes, the production of cytokines and Ig, and some mechanisms responsible for its regulating effect on lymphocyte-functions. Monocytes, CD 4^+, CD 8^+' and lymphocytes was isolated from the pheripheral mononucleus cell of healthy person, their proliferation, differentiation and the production of cytokine and Ig by EGF was measured. Also, the effect of cell, prostaglandin E_2(PGE_2), IFN-γ and some interleukin(IL) on the proliferation and differentiation of mononucleus cell was measured by using sensitive cell such as CTLL 2, mouse thymocytes, B9 cell, Wish cell. 1. When EGF was added to culture during the programming stage of activation, EGF inhibited the proliferative responses of periperal blood mononuclear cells significantly. 2. The responses were somewhat augmented if EGF was added to culture after mitogen activation, and were not influenced if EGF was added before activation. 3. The poke weed mitogen(PWM)- induced proliferative responeses of purified CD 4^+ and B lymphocytes were slightly decreased when EGF was added at 24hr after mitogen-activation. 4. The modulating effect of EGF on lymphocyte proliferation was time and dose dependent, and the potent suppression was manifested only when CD 4^+ cells and B lymphocytes were cocultured with monocytes and CD 8^+ cells. 5. The differentiation of CD 8^+ surppressor cells in PWM-stimulated cultures required soluble factors elaborated by CD 4^+ cells and monocytes. 6. EGF did not influence the differentiation of CD 8^+ cells directly, and EGF-induced augmantation of CD 8^+ cell-differentiation was developed through enhanced cytokine production of monocytes and CD 4^+ cells. 7. The monocyte-signal for such differentiation could be replaced not by ILI but by PGE_2, and the CD 4^+ cell-signal, not by IL2 but by interferon gamma. 8. By exposure of cells to EGF, ILl production of monocytes, 1L2 and IFN-γ production of CD 4^+ cells were significantly enhanced, but IL6 production of Staphylococcus aureus Cowan 1(SAC)-activated B cells was markedly down-regulated. IgG secretion of SAC-activated B cells was remarkably decreased by adding EGF to culture at initiation. 9. If exogeneous IL6 was added to cultures, Ig-secretion of EGF-B cells was significantly increased than that of EGF-free control. When fractionated B, cells were cultured in the presence of exogeneous IL6, IgG secretion of high-density small B cells was not influenced by EGF, but Ig secretion of low density large cells in EGF-group was significantly enhanced than that of control. l0. EGF did not alter the IL 2-dependent CTLL 2 cell- responsiveness to IL2, but it did greatly increase the responsiveness of target(B9) cells to 116 with about two-fold increment. These results suggested that EGF has multiple effects on event controlling lymphocyte-functions in a time-dependent manner via modulation of releasing soluble factors.