16. Section for Studies on Host-immune Response

The research activities currently being carried out in our section can be divided into two areas. The first is the study of an oxido-reduction enzyme, thioredoxin, a study that has continued since 1985. The second is the establishment of several cell lines of extrathymic T lymphocytes by transplanting surgical specimens of inflammatory breast cancer. This second study is in a newly developing field.

Thioredoxin and Its Role in Cell Activation

Thioredoxin is an oxido-reducing enzyme and historically this molecule is considered an essential molecule for DNA synthesis. For instance, it is reported to be an activator of ribonucleotide reductase and a subunit of the DNA polymerase of T7 phage. It was found that an Epstein-Barr virus-positive B-cell line predominantly produces an IL-1-like growth factor. In collaboration with Professor J. Yodoi's group at Kyoto University, this factor was successfully purified, cloned and found to be a human counterpart of thioredoxin according to the homology and highly conserved region of the enzymatically active site. Recombinant human thioredoxin was found to promote cell growth in synergy with several cytokines, such as IL-1 and IL-2. The role of thioredoxin in the second messenger signal transduction during the cell activation process has been studied and this factor was found to promote the proliferation of human B-cells through a protein kinase C-dependent mechanism.(202)

Development of T-cell Lymphomas of Extrathymic Origin after Implantation of Human Inflammatory Breast Cancer in BALB/c Nude Mice

Five independent tumors developed in BALB/c nude mice after xenografting of surgical specimens from five different inflammatory breast cancer patients. Several analytical procedures indicated that these tumors are of mouse origin. Histological examination revealed that the tumors of transformed mouse cell lines had features of malignant lymphoma. Phenotypically, the tumor cells expressed early T lymphocyte markers. This system might provide a good model for studies in several areas: in vivo malignant transformation, preferential metastasis to the organs and extrathymic T-cell development.


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