The differentiation and specificity of human CD4 T follicular helper cells (T cells) after influenza vaccination have been poorly defined. Here we profiled blood and draining lymph node (LN) samples from human volunteers for over 2 years after two influenza vaccines were administered 1 year apart to define the evolution of the CD4 T cell response. The first vaccination induced an increase in the frequency of circulating T (cT) and LN T cells at week 1 postvaccination. This increase was transient for cT cells, whereas the LN T cells further expanded during week 2 and remained elevated in frequency for at least 3 months. We observed several distinct subsets of T cells in the LN, including pre-T cells, memory T cells, germinal center (GC) T cells and interleukin-10 T cell subsets beginning at baseline and at all time points postvaccination. The shift toward a GC T cell phenotype occurred with faster kinetics after the second vaccine compared to the first vaccine. We identified several influenza-specific T cell clonal lineages, including multiple responses targeting internal influenza virus proteins, and found that each T cell state was attainable within a clonal lineage. Thus, human T cells form a durable and dynamic multitissue network.