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

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.

Immunoglobulin A in the epithelium of the respiratory tract and intrahepatic bile ducts of fetuses and newborns with pneumonia and sepsis.

The level of different immunoglobulins (IgA, IgG, IgM) in the tissues of 28 late fetuses and newborns was studied with peroxidase-labeled monoclonal antibodies. IgA+ and IgM+ lymphocytes were found in the spleen, lymph nodes and sometimes in the liver. IgG+ lymphocytes were not found. A high level of IgA+ material was found in the epithelium of the trachea, the epithelium and submucosal glands of the bronchi, but not the bronchioles, and in the epithelium of hepatic bile ducts and in their lumina. Such IgA is considered to be secretory--sIgA. Secretory IgA-containing epithelial cells appeared at 20 to 21 weeks of gestation; their number increased from 2.5 cells/10,000 microns2 in 23- to 26-week-old fetuses, to 8 cells/10,000 microns2 in 36- to 40-week-old fetuses. Secretory IgG and IgM were not detected. In fetuses with pneumonia or sepsis, the number of IgM+ and IgA+ lymphocytes increased significantly. IgM+ lymphocytes appeared not only in the spleen and lymph nodes, but also in the lungs. In such cases, the number of sIgA-containing epithelial cells in the trachea, bronchi and intrahepatic bile ducts decreased, sometimes completely disappearing. The amount of IgA+ material in the lumina of these organs increased, reflecting an intensification of sIgA secretion during infections. The presence of a marked amount of sIgA in fetuses from week 20 of gestation is considered to reflect the high importance of this immunoglobulin against normal contamination by microbes after birth, and to evidence the early maturation of the immune system.

Role of apoptosis, proliferating cell nuclear antigen and p53 protein in the immune response of rat colon cells to cancer and vaccination with anti-p53 polyclonal antibodies.

BACKGROUND: Previously it was shown that rabbit anti-p53 antibodies can exert tumor-suppressive effects on chemically induced rat colon cancer (Cancer J, 10:116-120, 1997). This work examines the role of some components of the immune system in the response of the rat colon cells to treatment with a carcinogen and anti-p53 antibodies. METHODS: 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. The manifestation of apoptosis, proliferating cell nuclear antigen (PCNA), mitotic index, T lymphocytes and p53 protein was compared between the different groups of rats. RESULTS: The apoptotic index and the number of p53-positive cells and T lymphocytes were significantly higher in colon adenocarcinomas obtained from vaccinated rats than in unvaccinated rats. PCNA was lower in tumors from the vaccinated rats, whereas the proliferating cell index was not different between the both groups of rats. An inverse relationship was seen between apoptosis and most other parameters studied. The inverse correlation found between apoptosis and p53 protein in this study demonstrated that apoptosis acts as a p53-independent parameter in chemically induced rat colon cancer. CONCLUSIONS: Our findings demonstrated that vaccination significantly activated apoptosis in both types of colon tissue, and induced synthesis of p53 protein in tumor tissue. Vaccination with anti-p53 polyclonal antibodies seemed to activate the immune system and to stimulate some of its cellular components responsible for tumor suppression.