Levels of the pro-apoptotic molecule Bim are determined early in the response and positively correlated with memory T cell fate (LYM5P.702)

Abstract

Abstract We and others have shown that the pro-apoptotic molecule Bim plays a critical role in controlling the contraction of T cell responses. Paradoxically, T cells destined to become memory (pre-memory) cells have higher levels of Bim than their effector counterparts. Similarly, after memory development, central memory (TCM) cells have higher levels of Bim relative to their effector memory (TEM) counterparts. However, due to the intracellular location of Bim, sorting and subsequent tracking of T cells based on Bim expression has been challenging. To circumvent this issue and determine the relationship between Bim expression and cell fate, we generated Bim-mCherry reporter mice, inserting an IRES-mCherry cassette into the 3’-UTR of the Bim gene. Similar to intracellular staining for Bim, mCherry levels were higher in pre-memory cells and TCM cells than their effector or TEM counterparts. In addition, the expression and function of Bim in T cells is not altered in Bim-mCherry reporter mice. The transfer of Bimhi or Bimlo T cells on the basis of mCherry expression favored their development into TCM or TEM cells, in recipient animals, respectively. Further, the levels of mCherry (and Bim) remained stable in the transferred mCherryhi or mCherrylo T cells across contraction of the response. These data suggest that the levels of Bim in CD8 T cells are determined at an early stage of infection and are paradoxically positively correlated with T cells having a memory fate.