Description:
<jats:title>Abstract</jats:title>
<jats:p>Highly differentiated CTLs make large quantities of proinflammatory cytokines and contribute to high mortality rates during influenza virus infections. Some pathogens trigger robust responses by short lived effector CD8 T cells (SLECs) which express KLRG1 but not CD127. Other less differentiated CD8 T cells which lack KLRG1 and quickly regain CD127 expression are better equipped to avoid deletion which led to the designation memory precursor cells (MPECs). Recent studies have shown that influenza virus-specific CTLs do not adhere to this pattern, since very small numbers of virus-specific CTLs acquired the KLRG1+CD127- phenotype during the peak of the effector response. We show that exposure to TGF-β during antigen stimulation greatly increases the size of the CTL response and changes the balance between the numbers of MPECs and SLECs during primary and secondary influenza virus infections. We reveal a dichotomy in the response to TGF-β which develops as the virus-specific CTLs become more differentiated. Our data suggest that TGF-β protects the lungs from immune damage through widespread depletion of SLECs, while simultaneously helping less pathogenic virus-specific CTLs colonize the mucosa where they can enhance to response to repeated viral infection.</jats:p>