Heterogeneous T cell subsets in both acute and chronic infection are possibly driven by a similar mechanism. (A) In acute infection, depending on T cell activation and inflammation intensity, heterogeneous MP cells are formed with various levels of CX3CR1, which give rise to diverse memory subsets. KRLG1^hi IL-7Ra^hi or exKLRG1 MP cells develop memory cells of higher cytotoxicity (Herndler-Brandstetter et al., 2018; Olson et al., 2013). (B) Several memory subsets maintain plasticity, which allows homeostatic (T_RM to T_CM; T_EM or T_PM to T_CM) or antigen rechallenge–induced (T_CM to T_EM, T_PM, or T_RM) cell state conversion (Marzo et al., 2005, 2007; Beura et al., 2018b; Park et al., 2018; Osborn et al., 2019; Fonseca et al., 2020; Frizzell et al., 2020; Wherry et al., 2003b; Wherry and Ahmed, 2004; Bouneaud et al., 2005; Gattinoni et al., 2011; Gerlach et al., 2016). (C) Parallel differentiation ontology in chronic infection. Tex_prog cells diverge from EE due to TOX and Tcf7 activation, which suppresses TE-like cell formation. Tex_prog further differentiate in a linear manner, or also perhaps in a bifurcated manner, to Tex_int or Tex_term cells. (D) Transcription gradient model for both acute and chronic infection. Shared TF gradients and surface receptors are found that drive the proliferative, stem cell–like cell states to more terminally differentiated cell states with effector function. KRLG1 expression is found in TE in acute and TE-like cells in chronic LCMV clone 13 and exhausted cells in HIV-infected patients. N, naive; SLO, secondary lymphoid organs.