CD4+T细胞亚群对树突细胞功能的反向调控作用及机制

Dendritic cells as a professional antigen-presenting cells play key roles in activation or tolerance of CD4+ T cell. At present, DC was focused on research in its function on antigen-presentation and activation CD4+ T cell and rare investigation were performed in the effects of CD4+ T cell on DC. In the present study, we analyse the phenotype and surface molecules expression of the dendritic cells isolated from the control and OVA immunised BALB/c mice, the mice depleted CD4+T cell with specific antibody and nu/nu naked mice. Then the effects of CD4+T cell on the development or phenotype of DC were studied when were cocultured with CD4+ T cell in vitro. Without OVA immunization, dendritic cells isolated from control mice , CD4+T cell depleted mice or nu/nu naked mice express no difference in CD11c,CD40,Fas, and H-2Kd , and lowly express CD40,Fas, and B7.1-2. In the OVA immunized mice, dendritic cells from nu/nu mice or CD4+ T cell depleted mice express much lower molecules than that from the OVA immunized control mice, and high Fas expression but lower apoptosis could be observed. Cocultured with different proportion of CD4+ T cell in vitro, the DC from CD4+ T cell depleted or nu/nu mice can express high levels of B7.1-2, H-2Kd, CD40,ICAM-1 and CD11c,and high apoptosis could be detected in the presence of high proportion of CD4+ T cell but low apoptosis could be observed in the presence of low proportion of CD4+ T cell. Although DC also express high H-2Kd when cocultured with irradiation inactivated CD4+ T cell, B7.1,2 ,ICAM-1, CD40,CD11c expression were much more lower compared with the DC cocultured with CD4+ T cell, but Fas was also high expressed.. Those results suggested that CD4+ T cells could exert their effects on DC reversely and regulte the function of DC. In immune reconstruction model, lethally irradiated SCID mice were survived after infused with CD4+T cell and dendritic cells at proper proportion, and niehter dendritic cells nor CD4+T cell alone prolong the survival time of the mice significantly. Those results suggested that CD4+ T cell could control the development and phenotype of dendritic cells in vitro and in vivo.

DC作为一种抗原递呈细胞与T细胞的激活与耐受密切相关。目前人们多从DC激活T细胞的角度来研究其功能，而对T细胞如何反向调控DC研究极少。本课题拟研究Th亚群对DC的反向调控饔茫教制涠訢C的发育成熟、功能维持、体内存活及凋亡的控制；分析反向调控的途径、毙А⒘啃Ч叵导敖峁üδ芨谋浼岸悦庖呦赴淖饔茫狣C功能完整性研究提供新思路