Functional Plasticity in Memory T Helper Cell Responses

Following activation, naive CD4+ Th cells can differentiate to selectively produce either the Th1 lineage-specific cytokine IFN-gamma or the Th2 cytokine IL-4 and, in so doing, lose the capacity to produce cytokines of the alternative lineage. Lineage commitment of murine CD4+ T cells has largely been considered to be absolute with little flexibility to produce cytokines of the opposing lineage. In this study, we demonstrate that cells within Th2 memory populations can produce IFN-gamma if reactivated in vivo in the context of an innate response that favors Th1 cell development. Likewise, cells within Th1 memory populations produce IL-4 when challenged under conditions that promote Th2 responses. Both effector and unpolarized central memory cells retain the potential to produce cytokines that were not made during the primary response. These findings reveal that both effector and central memory Th1 and Th2 cells possess the capacity to respond to environmental cues to produce pathogen-appropriate cytokines of the opposing lineage.