During acute T cell responses, the pro-apoptotic BH3-only molecule Noxa controls
high-affinity effector CD8 T cell formation via the elimination of activated low-affinity T
cells but it is unknown if Noxa deficiency also influences secondary T cell responses. In this
study we elucidated the role of Noxa in memory T cell formation and reactivation during
acute and chronic infections. In Noxa-/- mice, influenza infection resulted in an enlarged
memory T cell compartment which contained cells of increased clonal diversity and reduced
affinity. Re-infection caused strong effector T cell expansion of predominantly high affinity
cells. Chronic mCMV infection also resulted in a loss of initial affinity differen... More
During acute T cell responses, the pro-apoptotic BH3-only molecule Noxa controls
high-affinity effector CD8 T cell formation via the elimination of activated low-affinity T
cells but it is unknown if Noxa deficiency also influences secondary T cell responses. In this
study we elucidated the role of Noxa in memory T cell formation and reactivation during
acute and chronic infections. In Noxa-/- mice, influenza infection resulted in an enlarged
memory T cell compartment which contained cells of increased clonal diversity and reduced
affinity. Re-infection caused strong effector T cell expansion of predominantly high affinity
cells. Chronic mCMV infection also resulted in a loss of initial affinity differences between
WT and Noxa-/- T cells over time and to enhanced effector T cell accumulation in peripheral
organs. In a transgenic model of persistent T cell activation, effector T cell accumulation
ultimately led to severe organ pathology and premature death. These results establish the proapoptotic
molecule Noxa as an important regulatory molecule of effector population size
during recall responses. Absence of this molecule leads to excessive effector cell formation
and clinical consequences of deregulated immune activation.
