Interleukin-2 expression by a subpopulation of primary T cells is linked to enhanced memory/effector function

Single cell studies have identified intraclonal heterogeneity of cytokine p roduction by activated T cells. To investigate implications of cytokine het erogeneity for cell fate, an interleukin (IL)-2 promoter-green fluorescent protein (GFP) reporter transgenic model was developed to track IL-2(+) and IL-2(-) T cells during differentiation from naive precursors. Antigen-activ ated IL-2(+) and IL-2(-) cells had comparable proliferative capacities in p rimary responses. However, T cells that expressed IL-2 in primary responses demonstrated enhanced antigenic sensitivity and increased expression of ef fector cytokines in secondary responses in vitro and in vivo. Thus, heterog eneity of activation during a primary response translates into heterogeneou s secondary responses, in which enhanced memory/effector function is linked to cells that previously exceeded an activation threshold associated with IL-2 gene transcription.