Differences in Bcl-2 expression by T-cell subsets alter their balance after in vivo irradiation to favor CD4+Bcl-2hi NKT cells.
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-2(hi) NKT cells. Reduction of the Bcl-2(lo) mature T-cell subsets was at least 100-fold greater than that of the Bcl-2(hi) 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.
Yao
Zhenyu
Z
Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305-5166, USA.
Liu
Yinping
Y
Jones
Jennifer
J
Strober
Samuel
S
D000818:Animals; D006086:Graft vs Host Disease / Q000276:immunology* / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D014916:Whole-Body Irradiation; D051028:bcl-2-Associated X Protein / Q000276:immunology / Q000378:metabolism; D051020:bcl-X Protein / Q000276:immunology / Q000378:metabolism
C494812:Bcl2l1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D015847:Interleukin-4