CTLA-4 sensibilisiert T Zellen für Migration

Für eine optimale Immunantwort müssen T Lymphozyten zur richtigen Zeit am richtigen Ort sein. Über Dendritische Zellen stimulierte T Lymphozyten exprimieren verstärkt CTLA-4 (CD152). Signale über CTLA-4 sensibilisieren T Zellen sowohl an sekundär lymphytische Organe als auch zu einem Entzündungsherd in vivo zu wandern. In diesem Projekt soll die Signaltransduktion der CD152-initiierte Migration ermittelt werden.

Successful T cell immunity requires lymphocytes to be at the right time at the right place. The coreceptor CTLA-4 acts as a major check-point of the immune response, but the mechanism by which CTLA-4 controls peripheral T cell responses is unknown. Using sensitive liposome technology and migration assays, we show that only professional APCs namely mature dendritic cells were potent at inducing surface CTLA-4 expression and CTLA-4-mediated migration signals. CTLA-4 enhanced especially murine Th1 cell migration along chemokine gradients and increased functional expression of the chemokine receptors CCR5 and CCR7. Importantly, CTLA-4-mediated signals amplified  Th1 cell migration  to lymph nodes and an inflammatory site indicating a new and unexpected role for CTLA-4 in the orchestration of effector T cell localization to sites of inflammation and antigenic challenge.