Frontline: An in-depth evaluation of the production of IL-2 by antigen-specific CD8 T cellsin vivo

Abstract
IL‐2 is an important cytokine that is capable of inducing both proliferation and apoptosis of activated T cells. CD4 T cells are thought to be the major producers of IL‐2, but CD8 T cells also produce copious amounts of this cytokine. However, our current understanding regarding the kinetics of IL‐2 production by antigen‐specific CD8 T cells, and the proportion of these cells that produce IL‐2 in vivo, is extremely limited. We now demonstrate that virus‐specific CD8 T cells initiate IL‐2 production by 6 h post‐infection and prior to cell division in vivo. Interestingly, peak levels of IL‐2 production were achieved very early during the response and prior to the proliferative peak. We also show – using transgenic mice expressing herpes simplex virus‐1 thymidine kinase under the control of the IL‐2 promoter – that, unlike what has been reported for antigen‐specific CD4 T cells, the majority of antigen‐specific CD8 T cells produce IL‐2 during primary as well as secondary immune responses in vivo.