Impaired thymopoiesis occurring during the thymic involution of tumor-bearing mice is associated with a down-regulation of the antiapoptotic proteins Bcl-XL and A1

  • Authors: Roberto Carrio, Diana M. Lopez
  • View Affiliations

  • Published online on: Thursday, January 1, 2009
  • Pages: 89-98
  • DOI: 10.3892/ijmm_00000105

Abstract

The thymus is a central lymphoid organ in which T lymphocytes undergo differentiation and maturation without the need for antigenic stimulation. Apoptosis (programmed cell death), plays a critical role in shaping the T cell repertoire, deleting unproductive as well as potentially autoreactive T cells. Thymic atrophy has been observed in several model systems, including aging, graft-vs-host-disease and tumor development. However, the mechanisms involved in this phenomenon remain to be completely elucidated. We have previously shown that the progressive growth of D1-DMBA-3 mammary tumor leads to extreme thymic atrophy in the host. This thymic involution is associated with an early block in T cell maturation at the triple negative stage of differentiation. In the present study we have used our murine mammary tumor model to further analyze the specific T cell subpopulations present in the thymus of tumor-bearing animals as well as to characterize the alterations of the apoptotic process present during the impaired thymopoiesis associated to this thymic involution. Flow cytometric analysis revealed a moderate increase in the percentages of single positive CD4+ and CD8+ cells within the CD3 negative population in the thymuses of tumor-bearing mice. Moreover, we observed a prolonged increase in apoptosis among thymocytes from tumor-bearing mice compared with thymocytes from normal mice during tumor development. Lastly, we found a major decrease of Bcl-XL and A1, two crucial anti-apoptotic Bcl-2 family members that are developmentally regulated in T cells. Together, our data suggest that the severe thymic involution seen in mammary tumor bearers is due to an arrest in at least two steps of T cell differentiation and a down-regulation of important molecules that control programmed cell death.
Journal Cover

January 2009
Volume 23 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

2012 Impact Factor: 1.957
Ranked #26/121 Medicine Research and Experimental
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Carrio, R., & Lopez, D. (2009). Impaired thymopoiesis occurring during the thymic involution of tumor-bearing mice is associated with a down-regulation of the antiapoptotic proteins Bcl-XL and A1. International Journal of Molecular Medicine, 23(1), 89-98.
MLA
Carrio, and Diana Lopez. "Impaired thymopoiesis occurring during the thymic involution of tumor-bearing mice is associated with a down-regulation of the antiapoptotic proteins Bcl-XL and A1." International Journal of Molecular Medicine International Journal of Molecular Medicine 23.1 (2009): 89-98.
Chicago
Carrio, and Diana Lopez. "Impaired thymopoiesis occurring during the thymic involution of tumor-bearing mice is associated with a down-regulation of the antiapoptotic proteins Bcl-XL and A1." International Journal of Molecular Medicine International Journal of Molecular Medicine 23 no. 1 (2009): 89-98.