Singh Vinod, Agrewala Javed N
Institute of Microbial Technology, Sector 39A, Chandigarh-160036, India.
BMC Immunol. 2006 Aug 7;7:17. doi: 10.1186/1471-2172-7-17.
Presence of antigen presenting cells, expression of costimulatory molecules, the strength of first signal and cytokine milieu are quite important in influencing the reactivation of differentiated Th1 and Th2 cells.
In the present study, we have analyzed the concerted action of pro-Th1 and pro-Th2 cytokines in the presence of B cells, peritoneal and splenic macrophages as antigen presenting cells and varied concentration of first (anti-CD3 Ab) and second (B7-1 transfectant) signals on the proliferation and cytokine secretion by Th1 and Th2 cells. Interesting observations were made that IFN-gamma significantly augmented the secretion of IL-4 by Th2 cells when either B cells or splenic or peritoneal macrophages were used as APC. Further, IFN-gamma significantly inhibited the proliferation of Th1 cells only in the presence of peritoneal macrophages. We have also observed that B cells could significantly respond to cytokines to further enhance the proliferation and cytokine release by Th1 and Th2 cells. But not much effect on addition of exogenous cytokines IL-1, IL-4, IL-5, IL-12 was observed on the proliferation of Th1 and Th2 cells in the presence of macrophages. In contrast, both IFN-gamma and IL-2 significantly enhanced the production of IL-4 and IL-5 respectively, by Th2 cells in presence of B cells, splenic and peritoneal macrophages. Another important observation was that the addition of B7-1 transfectants in the cultures, which were stimulated with low dose of anti-CD3 Ab significantly, enhanced the proliferation and cytokine secretion.
This study indicates involvement of different type of APCs, cytokine milieu, dose of first and second signals in a concerted manner in the outcome of the immune response. The significance of this study is that the immunization with antigen along with costimulatory molecules may significantly reduce the dose of antigen and can generate better immune response than antigen alone.
抗原呈递细胞的存在、共刺激分子的表达、第一信号的强度以及细胞因子环境在影响分化的Th1和Th2细胞的再激活方面相当重要。
在本研究中，我们分析了在B细胞、腹膜和脾巨噬细胞作为抗原呈递细胞以及不同浓度的第一信号（抗CD3抗体）和第二信号（B7-1转染细胞）存在的情况下，促Th1和促Th2细胞因子对Th1和Th2细胞增殖及细胞因子分泌的协同作用。有趣的是，当使用B细胞或脾或腹膜巨噬细胞作为抗原呈递细胞时，干扰素-γ显著增强了Th2细胞分泌白细胞介素-4的能力。此外，干扰素-γ仅在腹膜巨噬细胞存在的情况下显著抑制Th1细胞的增殖。我们还观察到B细胞能够对细胞因子做出显著反应，从而进一步增强Th1和Th2细胞的增殖及细胞因子释放。但是，在巨噬细胞存在的情况下，添加外源性细胞因子白细胞介素-1、白细胞介素-4、白细胞介素-5、白细胞介素-12对Th1和Th2细胞的增殖没有太大影响。相反，在B细胞、脾和腹膜巨噬细胞存在的情况下，干扰素-γ和白细胞介素-2分别显著增强了Th2细胞产生白细胞介素-4和白细胞介素-5的能力。另一个重要的观察结果是，在低剂量抗CD3抗体刺激的培养物中添加B7-1转染细胞显著增强了增殖和细胞因子分泌。
本研究表明不同类型的抗原呈递细胞、细胞因子环境、第一和第二信号的剂量以协同方式参与免疫反应的结果。本研究的意义在于，与共刺激分子一起用抗原进行免疫接种可能显著降低抗原剂量，并且比单独使用抗原能产生更好的免疫反应。
