Agrewala J N, Suvas S, Singh V, Vohra H
Institute of Microbial Technology, Chandigarh, India.
Clin Exp Immunol. 2003 Oct;134(1):13-22. doi: 10.1046/j.1365-2249.2003.02254.x.
We have examined the possibility of evoking antigen-specific T cell immune response by using allogeneic cells as a source of adjuvant and also as a vehicle to deliver antigen. The mice were immunized with different preparations of antigen-pulsed allogeneic and syngeneic splenocytes. It was observed during the study that the animals immunized with antigen-pulsed mitomycin C treated allogeneic cells elicited antigen specific CD(4+) Th1 cell response. Predominant release of IL-2, interferon (IFN)-gamma and IgG2a-isotype also occurred. In contrast, mice immunized with antigen-pulsed syngeneic cells chiefly enhanced the production of interleukin (IL)-4 and IgG1-isotype. Further, allogeneic macrophages induced better T cell response than B cells or splenocytes and prominently induced the expression of B7-1 and B7-2. Immunization with antigen-pulsed macrophages provided better recall responses compared to B cells. This was manifested by the high LFA-1alpha and low CD45RB expression on T cells. Because it is already known that mitomycin C-treated cells undergo apoptosis and dendritic cells engulf apoptotic cells, we therefore propose that generation of T cell response using antigen-pulsed allogeneic cells may be due to the engulfment of these cells by dendritic cells, which may then process and present antigen entrapped in allogeneic cells to activate naive CD(4+) T cells and differentiate them to Th1 cells. This study therefore provides a rational basis for manipulating antigen-specific responses by immunizing with antigen-pulsed allogeneic cells.
我们研究了使用同种异体细胞作为佐剂来源以及作为递送抗原载体来引发抗原特异性T细胞免疫反应的可能性。用不同制备的抗原脉冲同种异体和同基因脾细胞对小鼠进行免疫。在研究过程中观察到,用抗原脉冲丝裂霉素C处理的同种异体细胞免疫的动物引发了抗原特异性CD(4+) Th1细胞反应。同时还出现了白细胞介素-2、干扰素(IFN)-γ和IgG2a同型的主要释放。相比之下,用抗原脉冲同基因细胞免疫的小鼠主要增强了白细胞介素(IL)-4和IgG1同型的产生。此外,同种异体巨噬细胞比B细胞或脾细胞诱导出更好的T细胞反应,并显著诱导了B7-1和B7-2的表达。与B细胞相比,用抗原脉冲巨噬细胞免疫能提供更好的回忆反应。这表现为T细胞上高LFA-1α和低CD45RB表达。由于已知丝裂霉素C处理的细胞会发生凋亡,且树突状细胞会吞噬凋亡细胞,因此我们提出,使用抗原脉冲同种异体细胞产生T细胞反应可能是由于树突状细胞吞噬了这些细胞,然后树突状细胞可能处理并呈递被困在同种异体细胞中的抗原,以激活幼稚CD(4+) T细胞并将其分化为Th1细胞。因此,本研究为通过用抗原脉冲同种异体细胞免疫来操纵抗原特异性反应提供了合理依据。