Bim mediates apoptosis of CD127lo effector T cells and limits T cell memory

Abstract

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‐7Rα) 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.