The fate of a mature, naïve T cell depends on the signals it encounters. Most naïve T cells perish within days or weeks after exiting the thymus, as they fail to bind to MHC-peptide complexes while scanning the surface of antigen-presenting cells (APCs) during their circulation through lymphoid tissues. To survive and differentiate into effector cells, T cells require two signals from activated dendritic cells: one through the T-cell receptor (TCR) and another via a costimulatory receptor, such as CD28.

The effector fate of an activated T cell is further influenced by a third category of signals—polarizing cytokines produced by APCs. These cytokines trigger the expression of master transcriptional regulators that direct the T cell to specific functions, including the secretion of effector cytokines. CD4 T cells, for instance, differentiate into various helper T-cell subsets such as Th1, Th2, Th9, Th17, and Tfh. These subsets collaborate with other cells to mediate type 1 and type 2 immune responses, characterized by distinct networks of helper T-cell subsets, effector cytokines, and other immune cell types like innate lymphoid cells (ILCs). Additionally, CD4 T cells can become regulatory T cells, which play a crucial role in suppressing autoimmune responses.

Activated T cells also develop into diverse memory cell subsets, which differ in their localization, circulation patterns, and effector functions. These memory cells enable the rapid effector responses observed during secondary immune responses. Despite advancements, significant questions remain regarding the origin, relationships, and molecular mechanisms underlying the development of these memory subsets.