Bim mediates apoptosis of CD127(lo) effector T cells and limits T cell memory.
Following an acute T cell response, most activated effector cells die, while some survive and become memory cells. The pro-apoptotic Bcl-2 family member, Bcl-2 interacting mediator of death (Bim) is critical for eliminating most effector T cells, while expression of CD127 (IL-7Ralpha) has been proposed to mark effector cells destined to become memory cells. Here, we examined the effects of Bim on the death of effector T cells in relationship to CD127 expression and on development of T cell memory following lymphocytic choriomeningitis virus (LCMV) infection. We found that large numbers of CD127(lo) LCMV-specific CD4(+) and CD8(+) T cells were lost in wild-type mice, but were spared in Bim(-/-) mice. Further, while the numbers of CD127(hi) T cells declined only slightly during contraction of the response in wild-type mice, they increased significantly in Bim(-/-) mice due to re-expression of CD127 on CD127(lo) T cells that had avoided apoptosis. Functional memory T cells were significantly increased in Bim(-/-) mice; however, they underwent a slow attrition due to decreased proliferative renewal. Taken together, these data suggest that the absence of Bim-mediated death of LCMV-specific CD4(+) and CD8(+) T cells in vivo can increase T cell memory, but other homeostatic mechanisms control the long-term maintenance of memory cells.
Wojciechowski
Sara
S
Division of Immunobiology, Cincinnati Children's Hospital and the University of Cincinnati, Cincinnati, OH 45229, USA.
Jordan
Michael B
MB
Zhu
Yanan
Y
White
Janice
J
Zajac
Allan J
AJ
Hildeman
David A
DA
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000072224:Bcl-2-Like Protein 11; D002478:Cells, Cultured; D007156:Immunologic Memory; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020395:Receptors, Interleukin-7 / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism* / Q000821:virology
D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D020395:Receptors, Interleukin-7