Differences in Bcl‐2 expression by T‐cell subsets alter their balance after in vivo irradiation to favor CD4+Bcl‐2hi NKT cells
Open Access
- 12 March 2009
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 39 (3), 763-775
- https://doi.org/10.1002/eji.200838657
Abstract
Although it is well known that in vivo radiation depletes immune cells via the Bcl‐2 apoptotic pathway, a more nuanced analysis of the changes in the balance of immune‐cell subsets is needed to understand the impact of radiation on immune function. We show the balance of T‐cell subsets changes after increasing single doses of total body irradiation (TBI) or after fractionated irradiation of the lymphoid tissues (TLI) of mice due to differences in radioresistance and Bcl‐2 expression of the NKT‐cell and non‐NKT subsets to favor CD4+Bcl‐2hi NKT cells. Reduction of the Bcl‐2lo mature T‐cell subsets was at least 100‐fold greater than that of the Bcl‐2hi subsets. CD4+ NKT cells upregulated Bcl‐2 after TBI and TLI and developed a Th2 bias after TLI, whereas non‐NKT cells failed to do so. Our previous studies showed TLI protects against graft versus host disease in wild‐type, but not in NKT‐cell‐deficient mice. The present study shows that NKT cells have a protective function even after TBI, and these cells are tenfold more abundant after an equal dose of TLI. In conclusion, differential expression of Bcl‐2 contributes to the changes in T‐cell subsets and immune function after irradiation.Keywords
Funding Information
- National Institutes of Health (NIAID RO1 AI-37683, NCI PO1 CA-49605, NHLBI RO1 HL-58250, NHLBI PO1 HL-57443)
This publication has 37 references indexed in Scilit:
- Augmentation of innate immunity by low-dose irradiationCellular Immunology, 2006
- A nonclassical non-Vα14Jα18 CD1d-restricted (type II) NKT cell is sufficient for down-regulation of tumor immunosurveillanceThe Journal of Experimental Medicine, 2005
- NKT cells are relatively resistant to apoptosisTrends in Immunology, 2004
- Anti-apoptotic Bcl-2 proteins: structure, function and relevance for radiation biologyInternational Journal of Radiation Biology, 2002
- CD1 Recognition by Mouse NK1 + T LymphocytesScience, 1995
- Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell deathCell, 1993
- p53 is required for radiation-induced apoptosis in mouse thymocytesNature, 1993
- bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytesCell, 1991
- Mixed chimerism and permanent specific transplantation tolerance induced by a nonlethal preparative regimen.The Journal of Experimental Medicine, 1989
- Transplantation of allogeneic bone marrow without graft-versus-host disease using total lymphoid irradiation.The Journal of Experimental Medicine, 1978