IL‐15 Induces Unspecific Effector Functions in Human Peptide‐Specific CD8+ T‐Cell Cultures

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Abstract
Antigen (Ag)‐specific CD8+ T cells are a major host defence against viral infections. In the present study, we generated human CD8+ T‐cell lines specific towards influenza matrix peptide (IMP)‐pulsed Ag‐presenting cells. We compared the effect of interleukin‐2 (IL‐2) and IL‐15 on the proliferation and cytotoxic activity of primary and secondary IMP‐specific cytotoxic T lymphocyte (CTL) culture. In primary CTL cultures, IL‐15‐induced cell expansion was considerably reduced as compared with IL‐2‐induced cell expansion, and IL‐15 favoured the outgrowth of CTLs without peptide specificity in these cultures.Secondary IMP‐specific CD8+ T cells were generated by the addition of IL‐2 during two cycles of restimulation. From the third restimulation, identical CTL cultures were expanded with either IL‐2 or IL‐15 in parallel. Cell expansion as well as Ag specificity was considerably reduced after a 5 day culture period in the presence of IL‐15. No or low CD69 expression was observed in IL‐15‐cultured CTLs, whereas IL‐2‐cultured CTLs contained high fractions of CD69+ cells. Furthermore, a high fraction of these latter cells coexpressed the cytotoxic marker CD56. However, IL‐15‐cultured CTLs exhibited cytotoxic activity without detectable expression of CD56, suggesting that CD56 is not essential for cytotoxic activity. Thus, the results presented suggest that IL‐15 favours the outgrowth of unspecific cytotoxic effector T cells.