大鼠脾细胞对致癌物及抗 p53 多克隆抗体疫苗接种的免疫反应。

Immune response of rat spleen cells to a carcinogen and to vaccination with anti-p53 polyclonal antibodies.

作者信息

Ben-Hur H, Gurevich P, Zion H, Berman V, Tendler Y, Sandler B, Zinder O, Zusman I

机构信息

Department of Obstetrics and Gynecology, Kaplan Hospital, Rehovot, Israel.

出版信息

Anticancer Res. 1998 Jan-Feb;18(1A):273-81.

PMID:9568090

Abstract

BACKGROUND

The tumor-suppressive effects of rabbit anti-p53 antibodies on chemically induced rat colon cancer were demonstrated previously (Cancer J, 10:116-120, 1997).

METHODS

In this communication, the spleen's role in the immune response of rats to cancer and vaccination was evaluated histologically and immunohistochemically. The following groups of rats were studied: a) control non treated rats; b) tumor-free non vaccinated rats treated with a carcinogen; c) tumor-bearing non vaccinated rats; d) tumor-free vaccinated rats exposed to a carcinogen; e) tumor-bearing vaccinated rats.

RESULTS

Exposure to a carcinogen (group 2) caused the appearance of the proliferative and apoptotic changes associated with immune response. They included abundant blast transformation of CD20-positive B lymphocytes, expansion of germinal centers and of periarterial sheaths (CD3-positive T cells), an increase in the number of plasma cells, mitotic and apoptotic cells in the follicles, and in CD25 IL2-depending T cells. The presence of colon tumors (group 3) caused insufficiency of the splenic lymphoid system: blast transformation was weaker, the white pulp area decreased and its devastation was reflected in fewer lymphoid cells. There were less plasma cells in the red pulp, while the number of dendritic cells, CD25+ T cells, macrophages and neutrophils increased sharply, suggesting a compensatory reaction to the severe antigenic effects. Similar, but stronger changes, occurred in tumor-free vaccinated rats (group 4). In tumor-bearing vaccinated rats (group 5), the rate of proliferation change was higher than in group 3, probably as a result of a weaker splenic insufficiency. A strong correlation was found between the number of mitotic, apoptotic or dendritic cells, tumorigenesis and vaccination.

CONCLUSIONS

A sharp increase in the number of dendritic cells in vaccinated tumor-bearing rats suggests that these cells participate in the host's reaction to tumorigenesis. We conclude that vaccination with anti-p53 polyclonal antibodies activates lymph components of the spleen.

摘要

背景

先前已证实兔抗 p53 抗体对化学诱导的大鼠结肠癌具有肿瘤抑制作用（《癌症杂志》，10:116 - 120，1997 年）。

方法

在本报告中，通过组织学和免疫组织化学方法评估了脾脏在大鼠对癌症和疫苗接种的免疫反应中的作用。研究了以下几组大鼠：a）未处理的对照大鼠；b）用致癌物处理的无肿瘤未接种疫苗的大鼠；c）有肿瘤未接种疫苗的大鼠；d）暴露于致癌物的无肿瘤接种疫苗的大鼠；e）有肿瘤接种疫苗的大鼠。

结果

暴露于致癌物（第 2 组）导致出现与免疫反应相关的增殖和凋亡变化。这些变化包括 CD20 阳性 B 淋巴细胞大量母细胞转化、生发中心和动脉周围鞘（CD3 阳性 T 细胞）扩张、浆细胞数量增加、滤泡中的有丝分裂和凋亡细胞以及 CD25 白介素 - 2 依赖性 T 细胞增加。结肠肿瘤的存在（第 3 组）导致脾脏淋巴系统功能不足：母细胞转化较弱，白髓区域减小，其破坏表现为淋巴细胞数量减少。红髓中的浆细胞较少，而树突状细胞、CD25 + T 细胞、巨噬细胞和中性粒细胞数量急剧增加，表明对严重抗原效应的代偿反应。在无肿瘤接种疫苗的大鼠（第 4 组）中发生了类似但更强烈的变化。在有肿瘤接种疫苗的大鼠（第 5 组）中，增殖变化率高于第 3 组，可能是由于脾脏功能不足较弱。在有丝分裂、凋亡或树突状细胞数量、肿瘤发生和疫苗接种之间发现了强烈的相关性。