Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>An effective CTL response is generally accomplished by massive CTL expansion and production of effector molecules, potentially exhausting resources and rendering the host vulnerable to other infections. It is not yet well known how the host maintains relative functional immunity against other pathogens during the course of an ongoing, robust CTL response against an active infection. We found that CTLs secrete exosomes in the presence and absence of IL-12, which all contain typical exosomal markers, such as ALIX and TSG101, as well as CTL proteins ZAP70 and granzyme B (GZB). However, when conditioned with IL-12, CTLs release smaller exosomes, which contain more proteins of exosomal markers, compared with exosomes secreted by control CTLs. More importantly, IL-12-conditioned exosomes can directly stimulate naïve CTLs to produce IFNγ, TNFα and GZB, which accompanied by upregulation of CD25, CD69 and CD44, independent of antigen or cytokines, whereas exosomes from control CTLs have minimal effects. In addition, IL-12-conditioned exosomes are able to strengthen weak TCR stimulation in CTLs. Proteomic analysis demonstrates that IL-12 stimulation skews exosomal proteins toward certain metabolism-related enzyme activities, including hydrolase, oxidoreductase and transferase, which are associated with CTL functions. Our findings indicate that the biological function and morphology of exosomes secreted by CTLs are influenced by the stimulation CTLs have received. This suggests that a functional, antigen-specific CTL response may boost functions of CTLs against other pathogens through secretion of functional exosomes. This may be a new mechanism for homeostatic regulation in CTL immune responses.</jats:p>