memory CD8 T cell Id(3)'d

The hallmark of an adaptive immune system is to respond more robustly when challenged again with the same antigen. It is called a memory response. CD8 T cells are the best studied model of antigen-specific CD8 T cell population expansion and contraction during antigenic challenge. Effector CD8 T cells that survive contraction phase form memory pool. It is estimated that only around 1-10% of a peak response CD8 T cells survive the memory bottleneck. Understanding the molecular mechanisms that allow a particular CD8 T cell to survive contraction phase will help to design better vaccination strategy. Many factors have been described that correlates (control) with memory CD8 T cells formation (for example, IL-7Ralpha or IL-2Ralpha expression). However so far no one came up with a clear model that could explain what controls the controllers. In my opinion, the answer will be found in the T cell receptor (TCR) specificity and in precise understanding how strength of signaling is translated into individual CD8 T cell fate.

If you interested to know more about mechanisms of CD8 T cell memory formation, I would recommend reading the following two papers recently published in Nature Immunology. Both papers, one by Cliff Yang et al. (1), and another by Yun Ji et al.(2), showed that the expression of transcription factor Id3 is necessary for memory CD8 T cells formation. Following data are critical for an analysis: in paper by Cliff Yang et al., Fig. 1e shows that expression level of Id3 is higher when increasing number of CD8 T cells are transferred. This may imply that Id3 is maintained more easily in CD8 T cells that receives minimal stimulation. Fig. 2B shows that Id3high CD8 T cells produce more IL-2 compared Id3low CD8 T cells. Fig. 3E shows that Id3high CD8 T cells are maintained in higher numbers upon adoptive transfer compared to Id3low CD8 T cells. Fig. 5A shows that Id3-deficient transgenic CD8 T cells (on wt background) are impaired in survival after viral infection compared to Id3-sufficient OT-I cells (3-fold reduction at day 60). In paper by Yun Ji et al., however, survival disadvantage of Id3-deficient transgenic CD8 T cells (on RAG KO background) is more pronounced compared to Id3-sufficient transgenic CD8 T cells. This may imply that TCR affinity (OT-I vs. pmel-1 or wt vs. RAG KO background) determines the absolute need for Id3 for memory formation.

David Usharauli