Toward a general model of CD4+T cell subset specification and memory cell formation

In the past few decades, a number of transformative discoveries have been made regarding memory CD8+ T cell biology; meanwhile, the CD4+ T cell field has lagged behind this progress. This perspective focuses on CD4+ helper T (Th) cell subset specification and memory cell formation. Here, we argue that the sheer num-ber of Th effector and memory cell subsets and a focus on their differences have been a barrier to a general model of CD4+ memory T cell formation that applies to all immune responses. We highlight a bifurcation model that relies on an IL-2 signal-dependent switch as an explanation for the balanced production of diverse Th memory cells that participate in cell-mediated or humoral immunity in most contexts.

Automated summary

In the field of CD4+ T cells, there has been a lack of progress compared to the transformative discoveries made in memory CD8+ T cell biology in recent decades. This perspective focuses on the specification of CD4+ helper T (Th) cell subsets and the formation of memory cells. The authors argue that the abundance of Th effector and memory cell subsets and the emphasis on their differences have hindered the development of a general model for CD4+ memory T cell formation applicable to all immune responses. They propose a bifurcation model based on an IL-2 signal-dependent switch to explain the balanced production of diverse Th memory cells involved in cell-mediated or humoral immunity.