当前位置： SCI文献检索 > Journal of Immunotoxicology期刊下所有文献 > Immune selection of tumor cells in TCR β-chain transgenic mice.

Immune selection of tumor cells in TCR β-chain transgenic mice.

Abstract：

:The concept of immunological surveillance implies that immunogenic variants of tumor cells arising in the organism can be recognized by the immune system. Tumor progression is provided by somatic evolution of tumor cells under the pressure of the immune system. The loss of MHC Class I molecules on the surface of tumor cells is one of the most known outcomes of immune selection. This study developed a model of immune selection based on the immune response of TCR 1d1 single β-chain transgenic B10.D2(R101) (K(d)I(d)D(b)) mice to allogeneic EL4 (H-2(b)) thymoma cells. In wild-type B10.D2(R101) mice, immunization with EL4 cells induced a vigorous CTL response targeted to the H-2K(b) molecule and results in full rejection of the tumor cells. In contrast, transgenic mice developed a compromised proliferative response in mixed-lymphocyte response assays and were unable to reject transplanted allogeneic EL4 cells. During the immune response to EL4 cells, CD8(+) T-lymphocytes with endogenous β-chains accumulated predominantly in the spleen of transgenic mice and only a small part of the T-lymphocytes expressing transgenic β-chains became CD8(+)CD44(+)CD62L(-) effectors. Then, instead of a full elimination of tumor cells as in wild-type mice, a reproducible prolonged equilibrium phase and subsequent escape was observed in transgenic mice that resulted in death of 90% of the mice in 40-60 days after grafting. Prolonged exposure of tumor cells to the pressure of the immune system in transgenic mice in vivo resulted in a stable loss of H-2K(b) molecules on the EL4 cell surface. Genetic manipulation of the T-lymphocyte repertoire was sufficient to reproduce the classic pattern of interactions between tumor cells and the immune system, usually observed in reliable syngeneic models of anti-tumor immunity. This newly-developed model could be used in further studies of immunoregulatory circuits common for transplantational and anti-tumor immune responses.

journal_name

J Immunotoxicol

journal_title

Journal of immunotoxicology

authors

Silaeva YY,Grinenko TS,Vagida MS,Kalinina AA,Khromykh LM,Kazansky DB

doi

10.3109/1547691X.2013.861548

subject

Has Abstract

pub_date

2014-10-01 00:00:00

pages

393-9

issue

eissn

1547-691X

issn

1547-6901

journal_volume

pub_type

杂志文章

在线工具

Immune selection of tumor cells in TCR β-chain transgenic mice.