Relationship between Th1 and Th17 polarization and maturational stage of Th memory cells. The initial polarization of naïve CD4⁺ T cells into the Th1 or Th17 subset not only induces a canonical set of transcription factors and cytokines but also affects CD4⁺ T-cell plasticity and fate. Th17 cells are relatively more plastic and less terminally differentiated than their Th1 cell counterparts. This is reflected by the higher ability of Th17 cells to self-renew, generate a distinctive highly functional Th1-like Th17 progeny, and form long-term memory following the secondary antigen experience. Th1 cells rapidly acquire a senescent phenotype and molecular signature, are less functional, and display less ability for self-renewal and memory formation. The lower panel demonstrates a proposed relationship between polarized CD4⁺ Th cells and a model of linear CD8⁺ T-cell memory formation. Upon antigen stimulation CD8⁺, T cells progress from naïve via self-renewing early memory stem cells (T_SCM), to central memory (T_CM and T_EM) cells, and to the senescent terminally differentiated cells with no self-renewal potential. In vivo antitumor efficacy of adoptively transferred cells used for immunotherapy of cancer inversely correlates with the maturational stage of T cells.