Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>CD8+ T cells are critical for protection against viral and intracellular bacterial infections. They are characterized by their ability to acquire cytolytic activity to lyse infected target cells. This effector stage is associated with the expression of a variety of intracellular and cell surface markers. Here, we examined the role of direct signaling by the cytokine IL-2 on the acquisition of CD8+ T cell effector functions. IL-2 signals via its heterotrimeric high-affinity receptor composed of the IL-2Rα-chain (CD25), β-chain (CD122) and common γ-chain (CD132). Previous work from our lab and others has shown that direct IL-2 signaling on CD8+ T cells is imperative for their differentiation into memory cells capable of secondary expansion. Using a mixed bone marrow chimeric approach in which wildtype (WT) and CD25 knockout (KO) cells are responding in the same environment we now demonstrate that KO CD8+ T cells are defective in effector differentiation following primary acute infection. CD25 KO effectors show decreased lytic activity and expression of effector-associated proteins and transcription factors, such as Granzyme B and T-bet. In addition, these cells show increased expression of naïve/memory-associated factors, such as Bcl2, Eomesodermin and IL-2 production, despite their inability to expand upon rechallenge. Overall, we conclude that direct IL-2 signaling is required for complete CD8+ T cell effector differentiation following infection in vivo.</jats:p>
<jats:p>This work was supported by the Howard Hughes Medical Institute and the National Institutes of Health Grant AI-19335 (to M.J.B.)</jats:p>