Differential Requirement of Beclin 1 for Regulating the Balance of Naïve and Activated CD4 + T Cells.

Autophagy is highly regulated and plays a multitude of roles during T cell-mediated immune responses. It has been shown that autophagy deficiency in T cells results in a decrease in total T cells, including naive T cells in young mice, but the mechanism is still not understood. Here, similar to what happened in young mice, we showed that T cell-specific deletion ofBeclin 1/Atg6(Becn1-/-) resulted in decreases in the percentages of CD4(+), CD8(+), and regulatory T cells in adult mice. In addition, we found that the effector to naive T cell ratio was increased in older mice. Also, as mice grew older,Becn1-/- mice progressively lost weight and developed severe colitis. Analysis of inflamed tissues demonstrated increases in the portion and cytokine production of effector T cells. In contrast, the TCR-transgenicBecn1-/- mice had similar numbers of naive T cells compared to WT controls. Similar to bulk T cells, the TCR-transgenicBecn1-/- T cells generated much lower numbers of effector T cells compared to WT controls after activationin vitro. These data suggest that autophagy is not required for maintaining the naive T cell but required for the generation of effector T cellsin vivo.